ANR Dokumentation Word 1018 EN-US

2018
ANR – Accelerated Neuro Regulation
1
Dr. med. Daniel Beutler, Thun
Pilot Project ANR Switzerland
«In the last 50 years, nothing has changed with regard to treating opioid dependency, because it was taken out of mainstream medicine...»
2
Dr. Andre Waismann
Barzilai University Medical Center, Ashkelon, Israel
1. Summary
4
2. ANR - explained for medical laypersons
4
3. Introduction
7
3.1
3.2
3.3
3.4
3.5
3.6
Opioid Dependency in Switzerland
Medication Assisted Treatment (MAT)
Opioid Analgesics
The costs of illegal drug use
Costs of Chronic Pain Disorders
Legal Basis
4. Scientific Basis
4.1 Opioid Receptors and Endorphins
4.2 Opioids and Opioid Dependency
4.3 Dependency and Addiction
5. History of ANR
5.1 Dangerous Experiments
5.2 Dr. Waismann
6. The ANR procedure
6.1
6.2
6.3
6.4
6.5
6.6
Information and Prior Clarification
Functional Principle and Treatment Process
Follow-Up Treatment
Psychosocial Follow-Up Treatment
Risks and Complications
ANR Schematic
7. The ANR Switzerland Pilot Project
7.1
7.2
7.3
7.4
7.5
7.6
7.7
Background
The Pilot Project in Detail
Results
Evaluation
Comparison with Conventional Withdrawal Procedures
Considerations on the "Scientific Character" of the Results
Future Prospects
7
7
8
9
9
10
11
11
13
14
15
15
16
17
17
18
19
20
21
22
28
28
28
29
32
33
35
36
8. Our experiences after five years of ANR treatments in the Spital Interlaken 37
9. Appendix
9.1
9.2
9.3
9.4
9.5
Interview with Dr. Waismann
About Dr. Waismann
Feedback from patients
Helpful Metaphors to Explain ANR
The ANR Treatment Team
48
49
54
56
64
67
3
1. Summary
ANR is a medication therapy for treating opioid dependency which was developed by Israeli
doctor and intensive care specialist Dr. Andre Waismann and has been successfully applied for
twenty years.
Primarily, a drug treatment on the level of opioid receptors in the brain is used to take corrective
action (neuroregulation), meaning in those brain structures which cause the dependency. A biochemical imbalance of the structures in the brain are pharmacologically remedied. The actual
withdrawal is almost a side product of this "intervention".
Opioids not only include illegal drugs like heroin or substitute medicines like methadone. The
periodic intake of medically prescribed strong pain medications, those known as opioid analgesics
such as morphine, can result in a dependency. Regular intake of opioids over longer periods of
time starts the adjustment mechanisms on the level of the opioid receptors in the brain. These
are processes that we have not yet been able to clarify in detail. Based on practical experience,
however, it can be assumed that the brain structures respond to the intake of opioids with an
increase in the number of receptors and possibly also with a change in the binding behavior.
The active ingredient Naltrexon has been known for over 20 years ago. As a so-called antagonist,
it does not have any separate (intrinsic) effect on the receptor but rather acts purely as a blocker.
To describe the interaction of opioids on the receptor as a lock and key principle, Naltrexon would
be like putting the wrong key in the lock – it fits, but it cannot open it.
A great deal of experimentation has been performed since the discovery of Naltrexon with the
idea of a blockade for the opioid receptors for the treatment of opioid dependency. Due to complications, and in view of the sobering results, this treatment has not yet become established in
addiction medicine. Dr. Waismann, the intensive care specialist, has been able to refine the ANR
treatment as part of his practical activities in such a way that the results turn out significantly
better and more long-term, and the safety could be improved as well.
To understand the treatment, it is important to make a clear distinction between dependency
and addiction. The former is an organic condition of the brain, potentially reversible, and therefore accessible by the ANR treatment. The latter is a psychological phenomenon and includes psychosocial deficits which have led to the use of substances and/or were caused or perpetuated by
them.
The pilot project ANR Switzerland started in 2012 with a trip to Israel. In the meantime, more
than 120 patients have been treated in Switzerland. The results are very good, and they not only
confirm the experiences of Dr. Waismann, but also verify that opioid dependency is not exclusively
a psychosocial problem. Rather, it is based on a reversible, treatable disorder of the brain function.
The treatment results of ANR to date justify the reweighing of the so-called four pillar principle
in addiction treatment medicine, in particular the "therapy" pillar which has decreased in importance due to sobering results with conventional withdrawal treatment in favor of "harm reduction". As a result, the abstinence goal would be strengthened but the resistance is great. On the
one hand, this is understandable in terms of skepticism of a method for which the evidence has
not yet been delivered according to strict scientific criteria. On the other hand, our results leave
no doubt that ANR must be further evaluated under scientific monitoring.
2. ANR - explained for medical laypersons
4
ANR is the abbreviation for Accelerated Neuro Regulation. ANR is more than "just" withdrawal.
ANR includes not only the actual withdrawal but also a re-adjustment of the nervous system,
namely those brain structures that play a role in dependency.
Our body is programmed such that it responds to external influences with the most stable and
balanced condition possible. This is done in the most efficient and energy-saving way possible,
and of course applies only to influences for which our body is also equipped.
For example, when we eat too many fatty meals, the volume of fat cells increases. With increased
alcohol consumption, the liver function and structure changes. When we spend too much time in
the sun, our skin stores more pigment. On the other hand, we are not prepared for the influence
of radioactive rays or certain chemicals so that our body's response is generally in the form of a
pathological disorder.
Opioid is the umbrella term for substances containing opioids, such as heroin, methadone, morphine, and related substances. Cocaine, cannabis, and other consciousness-altering substances are
not included.
Our body has a network of docking sites (= receptors) on which opioids can have an effect - like
the Rhine River which is dotted with countless docks between Basel and Rotterdam for ships to
load and unload cargo. This endogenous "opioid system" is the original place of effect for the
endo(mo)rphine (endo = inner; morphine = opioid). These endorphins are relatively well researched. They play an important role in regulating emotions and pain. They have a relaxing, anxiolytic effect, and in higher doses even relieve pain.
The effect of endorphins takes place in the dosage range of micrograms (millionths of grams).
The production and distribution of endorphins occurs from daily stimuli like physical, emotional,
and intellectual activities. Endurance athletes and stockbrokers reach the highest level of endorphin activities. As already mentioned, a sudden drop in endorphin stimulation can lead to emotional instability, for example "post-Olympic syndrome".
If opioids are taken from external sources, this is usually done in the milligram or even gram range.
The endorphin system adapts to this increased dosage, most likely by increasing the number and
density of opioid receptors or changing their sensitivity to opioids. This in turn means that more
and more opioids need to be taken to balance out the system.
This and the following concepts about the processes involving the opioid receptor system are
models and refer solely and exclusively to empirical values, meaning the clear scientific evidence
of these processes has not (yet) been fulfilled.
A useful image would be a small pond with goldfish where the fish are the opioid receptors and
the relatively modest amount of fish food is the everyday stimuli that are part of a balanced life. If
opioids are consumed on a regular basis and in larger amounts, this system expands, and the number of goldfishes increases significantly. The goldfish become predatory fish as the result of their
voracious hunger.
The amount of fish food (= opioid) increases correspondingly, which means that a relatively high
amount of opioids need to be consumed just to ensure that the system remains in balance (= predatory fish pond).
Physician and researcher Dr. Andre Waismann has successfully developed a treatment using the
receptor blocker Naltrexon, which has been known for many years, in which a type of muzzle is
5
slipped on to the predatory fish without affecting the original goldfish pond. This means that the
predatory fish decrease over time and the system is again returned to the natural state of a goldfish pond.
The (partial) blockade of the opioid system performed in the ANR treatment by displacing the
opioids from the receptors triggers an acute, very severe withdrawal. For this reason, the treatment must be done under anesthesia. The entire withdrawal is very condensed, meaning it is
shortened from about 4 to 5 weeks to only 5 to 6 hours! During this time the body endures all the
symptoms of withdrawal. This in turn explains the pronounced state of exhaustion that follows
immediately after the treatment.
In addition to the state of exhaustion, residual withdrawal symptoms take place in the first 48
hours: disorders of the gastrointestinal tract with diarrhea and intestinal cramping, short-term
cramping of the leg muscles, sleep disorders, and disorders of temperature regulation. These
symptoms improve immediately and simultaneously with the increase in the body's own endorphin within a few days, ending the initially pronounced malaise of the first two to three days.
These reports make clear why ANR is more than just a "withdrawal". Not only are the predatory
fish deprived, as with typical withdrawal, they are eliminated at an accelerated rate. A process
that would otherwise require several years has been shortened to only one to one and a half years.
This corresponds with the time during which the treated patients need to take Naltrexon in tablet
form to maintain the receptor blockade after the ANR treatment. Maintaining the blockade is absolutely critical for the success of the therapy and does not tolerate any experimenting. The therapy depends on reliable intake of Naltrexon. It is therefore not possible to stop Naltrexon for a
short period of time, consume opioids, and then start taking Naltrexon again. The patient's one
hundred percent cooperation, also called compliance, is key here.
The cooperation of the patient is also necessary to stimulate the endorphin production that has
been suppressed for years, or even decades, by opioid use. This can take a few days and requires
regular physical activity. It also helps to start return to a substantial diet as quickly as possible.
ANR is purely a medical intervention that is only able to remedy the dependency. Consumption
behavior that is not a "must", but instead is a "want" cannot be treated and requires psychological/psychotherapeutic guidance.
During the sustained Naltrexin intake period, the opioid system is blocked. Strictly speaking, during this period no relapse is possible. However, if Naltrexin is stopped in order to consume opioids, we are talking about the discontinuation of treatment, not a relapse, which in most cases
leads to a relapse.
6
3. Introduction
3.1 Opioid Dependency in Switzerland
The group of opioids includes morphine-like natural and synthetic substances of which heroin is
the most widely used drug. The results of the representative survey done in 2014 for Swiss citizens 15 years and older show that 0.7% of those surveyed have taken heroin at least once in their
lives. The percentage of persons with intake of heroin in the 12 months before the survey was
0.1%, similar to the percentage of those who used it within the last 30 days. Extrapolated across
the entire population, this corresponds with about 7000 people. An underestimate of the prevalence is however likely, since a social sanctioned behavior may not be disclosed in a telephone
survey, and those who are currently taking drugs can be difficult to reach by telephone.1
Estimates by the Federal Agency for Health (BAG) go from a total of 22,000 to 27,000 who are
opioid dependent in Switzerland. The number of new opioid addicts is rather regressive.
Based on data from the Canton of Zurich, it was shown that the highest level of prevalence for
heroin use was in the start of the 1990's – the time of open drug scenes – and from that point on
there has been a gradual decline.2
Illegal substances are used more often by men than by women. In addition, the use by adolescents
and young adults is higher than in the general population.
7
3.2 Medication Assisted Treatment (MAT)
Medication assisted treatment for opioid addiction is done with legal and guideline-compliant
prescription medications. The original goal was to bring about long-term drug abstinence in the
more or less foreseeable future or use a long-term substitution for the purpose of harm reduction
and thereby significantly improve the patient's health condition and social situation, while simultaneously preventing harm to society.3
Better results are expected when the substitute substance is administered with concurrent social
service and psycho-educative, or less often also with psychotherapeutic guidance. In addition,
medication assisted programs offer the possibility of providing clarification to the participants
concerning concomitant diseases (such as HIV and hepatitis), to provide treatment and to offer
immunizations against diseases such as Hepatitis A and B.
The substances used contain the indicated amount of active ingredient and no impurities. The
complications of intravenous drug use, such as needle abscesses and the transmission of Hepatitis C and B as well as HIV, can thereby be reduced. Those afflicted are also relieved of financial
and time burdens, and prostitution and drug-related crime can be reduced or avoided.4
In Switzerland, the most frequently used substitutes are methadone, buprenorphine, or delayedrelease morphine preparations, but Diaphine (heroin) is also used.
1
2
3
4
www.suchtmonitoring.ch
www.bag.admin.ch
Federal Agency for Health (German abbreviation BAG) Medication Assisted Treatment for Opioid Dependency, July 2013 Revision
Nosyk B, et al. Health related quality of life trajectories of patients in opioid substitution treatment.
Drug Alcohol Depend 2011; 118(2-3):259-264
In 2010, approximately 19,400 opioid addicts used medication assisted treatment (MAT); 85%
of them were treated with methadone.5 It is worth mentioning the historical background of methadone treatment, which can be traced back to research done by German doctors during the time
of the Second World War.6
The number of patients receiving medically prescribed heroin is about 1700, with a slight increase
over the last five years.7 It is concerning that ten years ago almost 80% of addicts had undergone
at least one attempt at withdrawal before starting prescription heroin; in 2014 this was the case
for less than 50% of addicts.8
It is noticeable that considerable amounts of means and resources have been invested in medication-assisted treatment in recent years. Thereby, the focus has been placed on the evaluation of
new substances (for example, time-release morphine preparations instead of methadone). Since
there is little evidence available for the conventional withdrawal procedure over the longer-term
course of treatment, and because the development of a tolerance after a withdrawal presents an
increased risk for overdose, the abstinence-oriented therapy pillar has been left in the background. It has even been postulated and integrated accordingly into the recommendations for established addiction medicine that an abstinence-oriented treatment should only be considered for
the minority of addicts.9
8
3.3 Opioid Analgesics
A survey in 2013 showed that when taking pain medication containing opioids, about 20% of
the population had taken such a medication in the course of the last 12 months. A comparison of
previous years shows a slight, insignificant increase in prevalence, as well as increased intake for
women and in the French-speaking regions.10 Newer figures also confirm a significant increase in
the course of the past years in Switzerland!11
The development of pain medication dependency is especially shocking in the USA, where it has
already taken on epidemic proportions.12 It is assumed that more than 100 US citizens die each
day from the consequences of pain medication consumption. The number of such deaths has doubled in just a few years. There are more deaths from pain medication in the USA than the total
number of deaths caused by heroin and cocaine. Such a development in Switzerland is currently
not anticipated, but it cannot be entirely ruled out, especially given the fact that the number of
patients with chronic pain has increased significantly in recent years.
Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement
therapy for opioid dependence (Review); The Cochrane Library, 2009, Issue 3
6 Ralph Gerlach: Methadone in Historical Context. From Discovery of the Substance to Maintenance
Treatment. Online publication: www.indro-online.de/methageschichte.pdf; Münster. INDRO e.V. 2004
7 www.suchtmonitoring.ch
8 Schweizer Institut für Sucht- u. Gesundheitsforschung [Swiss Institute for Addiction and Health Research]. Heroin-Assisted Treatment in Switzerland in 2014
9 Schweizerische Gesellschaft für Suchtmedizin (SSAM) [Swiss Society for Addiction Medicine]. Medical
recommendations for medication-assisted treatment for opioid dependency. 2006.
10 http://www.suchtschweiz.ch/infos-und-fakten/medikamente/einnahme/
11
www.ppsg.medicine.wisc.edu - The Board of Regents of the University of Wisconsin System.
12 CDC Online Newsroom; November 1, 2011; (404) 639-3286; Prescription painkiller overdoses at epi
demic levels. Kill more Americans than heroin and cocaine combined.
5
3.4 The costs of illegal drug use
Type of direct costs
in CHF
in %
Hospital and medical costs
Prevention and research
Therapies (inpatient and outpatient treatment)
Harm reduction and survival assistance
Repression
Direct costs for HIV/AIDS caused by drug use
Total direct costs for 2005
146,300,000
53,200,000
314,200,000
60,000,000
798’400'000
40,300,000
1,412,400,000.00
10.3
3.8
22.3
4.2
56.5
2.9
100.0
Jeanrenaud, Claude et al. (2005). Le cout social de la consommation de drogues illégales en Suisse
[The Social Cost of Illegal Drug Consumption in Switzerland].
The direct costs of illegal drugs in Switzerland are about CHF 1.4 billion annually, and the indirect
costs about CHF 2.3 billion. If you include the intangible costs of 400 million, the total costs
amount to CHF 4.1 billion annually.
It is obvious that every patient who receives sustainable treatment helps to save on these
costs – in every segment, including repression which is the cause of the highest costs!
Of particular note in this context are the factors the put extreme pressure on the costs, such as
treatment for Hepatitis C and HIV infections. Here the harm reduction has not had the success
hoped for, especially since the infections are acquired in a very early stage of drug use, meaning
often when sharing needles during the first use. In addition, based on our experience, nearly half
of the patients in a medication-assisted program regularly co-use an additional substance, which
in turn brings certain comorbidities with it.
3.5 Costs of Chronic Pain Disorders
Until 2005, only data from the USA was available and the costs in the European countries were
derived from this data. The first large European study "Pain in Europe" was published in 2005.13
With regard to pharmacotherapy for chronic pain, two opposing trends can be observed:
On the one side, the pain therapists have increased their warnings about the use of opioid analgesics, while on the other side the pharma industry has propagated the generous use of their newer
preparations.
Health economist Dr. HSG Willie Oggier analyzed the data for Switzerland. Based on his insights,
the economic costs (direct and indirect costs) in Switzerland are estimated to be CHF 4.3 - 5.8 billion annually.14
Harald Breivik, Beverly Collett, Vittorio Ventafridda, Rob Cohen, Derek Gallacher. Survey of chronic pain
in Europe: Prevalence, impact on daily life, and treatment. European Journal of Pain 10 (2006) 287–333
14 Bulletin des médecins suisses | Schweizerische Ärztezeitung | Bollettino dei medici svizzeri |
2007;88: 29/30 Page 1265
13
9
3.6 Legal Basis
The "Federal Law on Narcotics and Psychotropic Substances" (abbreviated as BetmG, revised version from October 1, 2012)15 puts legislative emphasis abstinence-oriented treatment on the
basis of the article of purpose.
In view of this, both the federation and the cantons are obligated to encourage research efforts in
this direction and use the fourth pillar of the four-pillar theory (therapy, prevention, harm reduction, repression) to strengthen it. Medication-assisted treatments are by definition not treatments, but instead belong to the principle of "harm reduction".
Article 1a:
"This law should prevent the unauthorized use of narcotics and psychotropic substances, namely by
the promotion of abstinence.”
Article 3d Para. 2:
Notes that it is the task of the canton to promote abstinence-oriented treatments, with the goal
of "creating conditions that make a drug-free life possible."
Article 3j:
Notes that as part of the research law from October 7, 1983, the federal government should "promote scientific research including the area of preventative and therapeutic measures."
10
15
https://www.admin.ch/opc/de/classified-compilation/19981989/201310010000/812.121.pdf
4. Scientific Basis
4.1 Opioid Receptors and Endorphins
The human body has structures in various organs which serve as a docking station for chemical
neurotransmitters. In so doing, signals are created which can influence a variety of body functions, including metabolic processes, thought processes, or psychological perceptions. These socalled receptors are present in almost all organs.16
The opioid receptors act as a docking station for the opioids.
In the brain there are many opioid receptors because the brain acts as a central switching station
and therefore has a regulating effect on all body functions. The original task of these opioid receptors is to act as a docking station for the body's own opioids – the endorphins. These endorphins,
to simplify somewhat, function as the "happiness hormone", meaning they have a largely euphoric, anxiolytic, and pain-reducing effect. They are also involved in many additional functions,
such as concentration, relaxation, temperature regulation, appetite, sleep, etc.
External opioids, or those acquired from outside of the body (drugs or other medications) differ
in their clinical effect in that they have a different affinity to the individual receptor types.
International nomenclature
μ
δ1
Pharmacological
nomenclature
OP3
Cloned receptor
MOR
Subtype agonists
DAMGO,
Sufentanil,
morphine
DPDPE,
DADLE,
SNC 80
Subtype
Antagonists
β-FNA,
CTAP,
CTOP
Endogenous
ligands
OP1A
δ2
κ
Orphan ORL1
OP1B
OP2
DOR
KOR
ORL1
DSLET,
Deltorphin
U-50,488H
U-69,593
CI-977
Nociceptin/
Orphanin
FQ
ICI-17,4864
Naltrindol,
BNTX
DALCE
Naltriben,
Naltrindol,
ICI-17,4864
nor-BNI
β-Endorphin,
Endomorphin-1
Endomorphin-2
β-Endorphin,
Leu-Enkephalin
Met-Enkephalin
β-Endorphin,
Leu-Enkephalin
Met-Enkephalin
Dynorphin A
Selective
antagonists
β-CNA,
Naloxon,
Naltrexon,
Cyprodime
β-CNA,
Naloxon,
Naltrexon,
Cyprodime
β-CNA,
Naloxon,
Naltrexon,
Cyprodime
β-CNA,
Naloxon,
Naltrexon,
Cyprodime
Effector
cAMP Modulation, cAMP Modulation, cAMP Modulation, cAMP Modulation, cAMP
Open K-channel, Open K-channel, Open K-channel, Open K-channel, Modulation,
Close Ca channel Close Ca channel Close Ca channel Close Ca channel Open K-channel,
Close Ca channel
Nociceptin/
Orphanin
FQ
Abbreviations: β-FNA =beta-funaltrexamine; beta-CNA = beta-chlornaltrexamine; CTOP = D-Phe-Cys-Tyr-D-Trp-Arg-ThrPen-Thr-NH2; CTAP = D-Phe-Cys-Thr-D-Trp-Om-Thr-Phe-Thr-NH2; BNTX = 7-Benzylidenennaltrexone; DALCE = [D-Ala2,
Leu5,Cys6]-Enkephalin; DAMGo = [D-Ala2, N-Me-Phe4,Gly-ol5]-Enkephalin; DESLET = [D-Ser2, Leu5, Thr6]-Enkephalin; norBNI = Norbinaltorphimine; Endomorphin-1 = Tyr-Pro-Trp-Phe-NH2; Endomorphin-2 = Tyr-Pro-Phe-Phe-NH2
Table 1: Summary of the most important opioid receptors having endogenous ligands and selectively bonding exogenous antagonists, as well as their relevant functions in the nerve cells.17
16
17
General and special pharmacology and toxicology. Urban & Fischer; ISBN 978-3-437-42523-3
Enno Freye. Opioids in medicine. Pabst Science Publishers, 9th Revised Edition.
11
µ1
µ2
κ
δ
Spinal/supraspinal
Analgesic
Spinal analgesic
Spinal/supraspinal
Analgesic
Spinal/supraspinal analgesic
Euphoria
Low dependency potential
Respiratory depression
High dependency potential
Dysphoria
Low dependency potential
Respiratory depression
High dependency potential
Bradycardia
Severe constipation
Myosis
Hyperthermia
Diuresis
Mild constipation
Urine retention
Table 2: Various opioid bonding locations and their pharmacological effects. 16
A particular form of endorphin release is the so-called "runner's high”, a feeling of happiness that
can be generated by physical activity such as long-distance running. It is also known that sexual,
intellectual, and emotional stimuli can cause an increase in the endorphins.18
An example for the opposite effect is known as the "post-Olympic effect", a phenomenon that can
affect athletes who end their career at its highest point. The elimination of the endorphin stimuli
(regular intense training, media presence, etc.) can result in some cases in severe depression.19
It is also known that people who tend to consume large quantities of alcohol show an innately
lower level of endorphins, however this can often be elevated to a somewhat excessive range by
the use of alcohol.20 On the other hand, alcohol withdrawal frequently leads to reactive depression
in these people, and it typically stops about three to six months after the withdrawal. In this context it is interesting that the opioid antagonist Naltrexin® shows good result for maintaining abstinence for those with chronic alcoholism.
Opioid receptors in organs other than the brain have a subordinate significance but are responsible for certain side effects of the opioids (for example, chronic constipation) when used on a regular basis.
It is especially worth noting at this point that the son of a patient who suffers from severe painrelated opioid dependency and was treated successfully with ANR, wrote an excellent senior thesis on the interaction of Naltrexon on µ receptors. This work is considered one of the best submitted in this area in the Canton of Bern.21
Henning Boecker et al. The Runner's High: Opioidergic Mechanisms in the Human Brain.
Cereb. Cortex (2008) 18 (11): 2523-2531.
19
Lucas Fischer. "After retirement, I fell into a hole." Berner Zeitung, May 14, 2016
20 Genazzani AR, Nappi G, Facchinetti F, Mazzella GL, Parrini D, Sinforiani E, Petraglia F, Savoldi F.
Central deficiency of beta-endorphin in alcohol addicts. J Clin Endocrinol Metab. 1982 Sep;55(3):583-6.
21
The μ opioid receptor and Naltrexon; senior thesis by J.W., Gymnasium Neufeld Bern, October 2017
18
12
4.2 Opioids and Opioid Dependency
Per the traditional definition, opioids are medicinal products that contain opium. In modern pharmacology, the term is generally used for opium alkaloids and the half-synthetic and non-peptide
pharmaceuticals derived from them. Morphine is the oldest and most relevant opioid and is considered a reference substance in pain treatment with which the pain-relieving effect of the other
opioids is measured.
Opioids also include those substances that are used as drugs (e.g., heroin), or as substitution
medication (e.g., methadone or buprenorphine).
To understand opioid dependency, it is important to know that opioids taken from external
sources are administered at much higher doses compared with endorphins and therefore have a
significantly stronger effect on the brain than the body's own endorphins. As a result, the regular
intake of opioids causes structural adaptation processes to occur in the brain. At the same time, it
does not matter whether illegal opioids, substitute medications, or medically prescribed pain
medications are involved.22
It is assumed that there is an increase in opioid receptors or a change in their affinity and sensitivity, resulting in a functional imbalance in the body's own opioid system. These processes are ultimately responsible for the dependency syndrome which manifests as an unquenchable craving
for the substance and withdrawal symptoms during abstinence.
ANR refers to the knowledge that the changes on the level of the endogenous opioid system
can be influenced by a targeted blockade of the excessive opioid receptors, and thus are reversible.
In addition to the mechanisms described, additional biochemical processes are involved in the
dependency and addiction events on the somatic level. An example is the similar central role of
dopamine metabolism.
On the psychological and psychosocial levels there are numerous mechanisms involved in the
usage behavior of opioid addicted people. As part of the previous treatments, it is our experience
that these factors are not decisive for opioid use in more than half of the cases.
The psychosocial deficits are often a consequence of the opioid use and dependency – and not
the cause!
Thus, in the medical history it can often be determined that people who grew up in a "normal"
environment, meaning they had a functional family and correspondingly unremarkable childhood
and youth experiences, generally have experience with the use of conscious-altering substances
not due to some kind of addiction-specific characteristic but almost always out of curiosity which
then develops into a dependency.
22
Freye E, Latasch L.; Tolerance Development While Taking Opioids – Molecular Mechanisms and Clinical
Significance; Anesthesiological Intensive Care Trauma Medicine Pain Treatment 2003; 38: 14-26
13
4.3 Dependency and Addiction
Based on our experience, opioid dependency has a somatic, or biochemical structural component
which can be influenced, meaning it is accessible to medical treatment. In addition, there is always
a counterpart to the psychological, not structurally tangible level. This distinction is not common
in established addiction medicine, and the terms dependency and addiction are generally used as
synonyms.
The difference between (somatic) dependency and (psychological) addiction behavior is an important characteristic for the essence of ANR treatment. This differentiation is vague and extremely individual but is critical for the success of the treatment, particularly since only the dependency can be treated with ANR.
Based on the bio-psycho-social model, this image still needs to be expanded with the "social"
component to be complete. Between these areas multiple interactions are possible.
A frequent observation that we make as part of gathering medical history for drug use is that the
first experiences with opioids came purely from a willingness to experiment, and it is only with
regular use that the foundation is laid for dependency (not an "addictive personality", as is often
assumed). Most drug addicts can almost say the day when this phenomenon occurred in them.
From this point in time, they no longer use opioids to feel "good", but rather to feel "not bad". Once
the dependency is established in this manner, secondary addictive behaviors often develop.
These processes are plausible in patients who undergo medication-assisted treatment due to
opioid dependency. In particular, when they experience a bio-psycho-social stabilization due to
more beneficial medical conditions and thus no longer have access to the drug scene and also no
longer keep up the co-use, a situation can arise where there is only a dependency and no more
addiction behavior.
Similar mechanisms occur with opioid-addicted pain patients. In this case, neither a willingness
to experiment nor an addictive personality is the reason for regular intake of opioids, but rather
the cause is medical. Nonetheless, a dependency occurs without any addiction behavior, which
can also develop into secondary addiction as well.
The best illustration offered for this model is the opioid-addicted newborn – the child of a
mother who used opioids during pregnancy. This is an almost exclusive dependency on the part
of the newborn, and addiction mechanism hardly plays a role. Nevertheless, there is of course a
social component in the sense that the child was born in to an "addicted family".
14
5. History of ANR
5.1 Dangerous Experiments
The opioid antagonist Naltrexon23 has been known for more than 20 years and experiments have
been conducted with it for just as long. At the same time, the goal was pursued to block the opioid
receptors in the brain with relatively high doses and thus treat the dependency. Due to insufficient
effectiveness, lack of sustainability, and in some cases, life-threatening complications, this treatment approach was repeatedly rejected, and the corresponding studies ended.
These experimental procedures are found in medical history books under the names "Rapid
Detox", "Ultra Rapid Detox (UROD)", "FOEN (forced opioid withdrawal under anesthesia)", "Sleeping Withdrawal", "Turbo Withdrawal", etc. All of these procedures were similar in that the majority of them were based on theoretical considerations and the implementation was attempted with
a strict mechanistic approach. The origins in the early 1990's often took place in psychiatric practices without an intensive care infrastructure, frequently resulting in serious complications or
death.24
Additional deficiencies included non-compliance with pharmacodynamic characteristics of the
antagonizing substance Naltrexon, which can cause severe circulatory disorders with intravenous
application. The scientific preparation of these experiments therefore led to the clear conclusion
that medicated withdrawal procedures under anesthesia had no benefit. Accordingly, in Switzerland they were also never included in the basic service catalog for insurance companies or were
explicitly excluded from them.25
Nevertheless, even with these methods a development could be seen in the course of recent
years. Similar to laparoscopic surgery, which achieved decidedly poor results in the first years due
to the length of the surgery, the withdrawal procedure under anesthesia under the umbrella term
"Rapid Opiate Detoxification (ROD)" or "Opiate detoxification under anesthesia" in some countries (like the US and Australia) were further developed and in some cases even used as the standard for the treatment of opioid dependency.
A study from Iran documented a 9-month success rate of 80% (!) for a UROD procedure. This result
could be explained for reasons including the socio-cultural framework in a country with a rigid drug
policy and without the "low threshold alternative" of a medication-assisted treatment.26
An additional study from the USA verified very good results for opioid-addictive burn victims.27
Pharma-kritik, Year 15 No. 17/1993
Gowing L, Ali R, White JM. Opioid antagonists under heavy sedation or anaesthesia for opioid withdraw
al. (Review) The Cochrane Library, 2010, Issue 1
25 André Schirtz, Robert Hämmig, Barbara Broers, Lukas Bösch, Rudolf Stohler;
SwiDeCo – Swiss Detoxification Coordination: A multi-centre project on the effectiveness of opiate detoxification in Switzerland; Suchtforschung des BAG 1999–2001
26
Naderi-Heiden A, Naderi A, Naderi MM, Rahmani-Didar F, Salimi AR, Gleiss A, Kasper S, Frey R.
Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.
Pharmacopsychiatry. 2010 Jun; 43(4):130-7.
27
Maani CV, DeSocio PA, Jansen RK, Merrell JD, McGhee LL, Young A, Williams JF, Tyrell K, Jackson
BA, Serio-Melvin ML, Blackbourne LH, Renz EM. Use of ultra rapid opioid detoxification in the treatment
of US military burn casualties. J Trauma. 2011 Jul;71(1 Suppl):S114-9.
23
24
15
5.2 Dr. Waismann
For the first time, the case of a severely opioid-addicted 6-year old boy brought the creator of ANR,
Dr. Andre Waismann, to the attention of the experts in the field. The case of this child, who had
received treatment with opioids for months after the removal of an astrocytoma, was presented
to the European Congress for Anesthesiology in 1998 in Frankfurt.28
Andre Waismann had originally experimented in the field with the controversial "Rapid Detox"
procedure, but quickly realized that this mechanistic approach was not expedient. In particular,
the knowledge that the complete blockade of the opioid system also paralyzed the endogenous
system for endorphins and that the patients then developed corresponding deficits in the emotional area required a new treatment approach. Thus, Waismann further developed and refined
the treatment as part of his many years of clinical work. The results turned out significantly better,
and complications could be largely eliminated.
One of the most important principles that was worked on in the process was the knowledge that
the receptor blockade needs to be handled individually, i.e., handled differently from patient
to patient. In so doing, the following factors must be taken in to consideration:
•
•
•
the duration and extent of the opioid intake before treatment
the response to the blockade under treatment
the adjustment of the consolidated receptor blockade after the treatment.
In the process, ANR was done from the very start only under intensive care conditions.
This essentially eliminated serious complications. Several thousand patients around the world
were treated with ANR and freed from their opioid dependency for the long-term.
28
Waismann A et al. Iatrogenic morphine addiction in a 6-year old child following resection of an
astrocytoma. Reversion with Naltrexone under sedative anesthesia. 10th European Congress of
Anesthesiology 1998 Frankfurt.
16
6. The ANR procedure
6.1 Information and Prior Clarification
In the beginning, there is detailed information about the procedure and the clarification of any
questions or misunderstandings that could result from a lack of clear distinction from purportedly
related procedures.
Collecting the medical history includes a detailed inquiry of the substances consumed. It is also
used to document any possibly relevant secondary illnesses, intolerances, or allergies to medications, and potential anesthesia procedure risks.
As part of a detailed psychiatric screening, the motivation for the treatment is examined and any
possible psychiatric co-morbidities and potential stumbling blocks are discussed. The psychosocial background, important biographical data, and resources for follow-up treatment are recorded
and documented as well.
Based on medical history and information from the referring party, a lab examination is ordered,
and a basic physical examination is done, including ECG and possible spirometry. Depending on
the findings from these evaluations, additional testing (x-rays, echocardiography, ultrasound, etc.)
is performed.
The previously mentioned clarifications and examinations are generally done two to three weeks
before the ANR treatment. A consultation with the responsible anesthesiologist involved with
the opioid withdrawal after the ANR in the hospital is also part of this process. In so doing, the
somatic medical history as well as that for the opioid dependency will be supplemented, if needed.
This procedure is explained again in detail, questions answered, and the risks clarified. If needed,
additional specialists are consulted.
The patient file is transferred to the ANR team in the hospital and to the patient's primary care
physician upon request.
A final consultation is held on the evening prior to the treatment. Generally, all the doctors involved and Dr. Waismann are present.
If there are no contraindications found in the pre-evaluations, examinations, and meetings, the
patient is admitted to the hospital on the day of treatment and prepared step-by-step for the ANR
procedure.
17
6.2 Functional Principle and Treatment Process
The ANR procedure includes four treatment steps:
First, an acidification of the metabolism is used to flush out the opioid reserves from the bones
and fatty tissues.
Second, a Naltrexon blockade – individually titrated depending on the history of substance abuse
– is used under anesthesia to regulate the opioid receptors.
Third, the endorphin system, which has been suppressed from external opioid intake, is stimulated again.
Fourth, Naltrexon is taken in tablet form during 12 to 18 months of consolidation treatment. Only
afterwards is the treatment concluded.
18
In the first five hours before starting the anesthesia, several substances are administered for
regulating the autonomic nervous system, to calm the brain, and to protect from aspiration in order to prevent large fluctuations in blood pressure, increase in pulse, and general stress reactions
and cramping, etc., during the withdrawal procedure.
At the same time, the patient's metabolism is acidified using ascorbic acid (vitamin C). This is
intended to mobilize and eliminate the opioids still present in the body (including in the fatty tissues and bones).
After the preparation time, the patient is transferred to the intensive care unit and the actual intervention is started by the anesthesiologist, meaning the intubation anesthesia is introduced
and the physical withdrawal is started. The patient is not aware of the withdrawal symptoms triggered by Naltrexon because they are under anesthesia during this time. The anesthesia is done
with propofol, which must often be given in high doses at the start of the physical withdrawal in
order assist the concomitant medicine in keeping all bodily functions in the normal range. The
depth of the anesthesia is selected such that the body's response to the receptor blockade can be
evaluated based on clinical criteria. Muscle relaxation is avoided, also to allow for clinical evaluation of the course of the treatment.
Patients receive two to three individually titrated doses of Naltrexon over five to six hours via
gastric tube. A circulation-stabilizing and sedating concomitant medication prevents severe heart,
circulatory, respiratory, or cerebral reactions. During the entire time in the intensive care unit
there is 1:1 care from the intensive care or anesthesia nursing staff. The anesthesiologist is always
on site. After ending the anesthesia and extubation, the patients remain in intensive care for another two to three hours for monitoring. After being transferred back to the normal ward, they
are monitored bedside throughout the entire night. During this night, the patient sleeps a great
deal; however, during the waking phase they are quite exhausted and unbalanced. This is understandable because the body is opioid free at this time – even without endorphins – and the stresses
of the ultra-short withdrawal are still having an effect.
Day 2 is for rest and recuperation and is used for treating the stomach and intestinal problems
that frequently occur. The patient still feels weak, sometimes still has calf pain, and often complains about blurred vision. Gradual Mobilization and Return to Normal Diet.
Day 3 - 5
The next morning, the patient is discharged to a hotel near the hospital to be accompanied by a
person they trust. The patient remains here for another two to three days. During this time, they
are regularly visited by Dr. Beutler/Dr. Waismann.
6.3 Follow-Up Treatment
On the day after the ANR procedure, the consolidation treatment is started with Naltrexon. This
treatment in the form of a tablet to be taken daily is extremely important. It ensures maintenance
of the receptor blockade and thus prevents a resurgence of the craving for opioids. Here the dosing
and duration of the Naltrexon treatment is done individually, generally ranging between 25 and
50 mg/day for a duration of 12 to a maximum of 18 months.
In contrast to the more typical "Nemexin program" (receptor blockade with Naltrexon after
prior conventional withdrawal), the introduction of Naltrexon after ANR has practically zero
side effects.
It is assumed that the opioid receptors occupied with Naltrexon degenerate with time under the
blockade and are no longer able to generate addictive signals – a process that can take five to ten
years without the ANR procedure and Naltrexon treatment. After carefully tapering the Naltrexon,
there is normally no appearance of any craving – the opioid dependency has been removed.
The compliance (cooperation by the patient) in taking Naltrexon is one of the keys to success of
the ANR treatment. As detailed below, most of the treatment that was discontinued as part of the
pilot project was the result of unreliable Naltrexon intake or stopping it too soon.
In the following days to weeks, the patients are instructed to return as quickly as possible to
their normal daily routine. Regular food intake and appropriate physical activity are extremely
important for the success of the treatment but can present a huge challenge for many (former)
opioid addicts.
19
There is a great deal of information indicating that the effects of years of opioid use, in certain
circumstances, can cause significant damage to the gastrointestinal tract. It is assumed that absorption of vitamins and other essential nutrients like minerals and trace elements can be reduced
to such a degree that multiple and in some cases irreversible damage can occur to the organism.
Depending on how severely the brain is affected by such deficiencies, these can form an aspect of
the addiction that is reflected in the typical stigmata (facies, motor skills, language). For this reason, a vitamin-enriched, balanced diet is of particular importance. This also presents a great challenge for the addict, depending on the psychosocial environment. Alternatively, nutritional supplements (such as JuicePlus®) can be used.
An additional key to treatment success is endorphin stimulation – in the words of Dr. Waismann,
"a life rich of endorphins". This includes not only regular physical activity, but also intellectual
stimuli, social interactions, and a sex life that is as active as possible. It is interesting to observe
how differently the people treated perceive this newly-awakened instrument for regulating their
disposition that had been suppressed while opioid dependent, in some cases for years or even
decades. The more mindfully the patients manage this stimulation of the endogenous opioids, the
more sustainable the success of the treatment.
After no longer than a year and a half, the Naltrexin is gradually tapered and discontinued. The
treatment is complete. Due to previous experience, there is reason to assume that the "excess"
opioid receptors degenerate under the blockade. For this reason, it is generally not a problem to
taper the Naltrexin blockade after this time has passed.
6.4 Psychosocial Follow-Up Treatment
20
To understand the method and the guidance for the patients treated, it is important to note the
strict differentiation between dependency and addiction (see also section 4.3). Dependency is
an insuppressible "hunger", so it is somatically triggered and therefore can be influenced on the
organic level. Addiction, on the other hand, is the (deliberately controllable) urge for a substance
or the "kick" or "flash" and is therefore more of a psychological phenomenon. This differentiation
is not made in established addiction treatment medicine.
Waismann's experience corresponds with our observations as part of the pilot project that in most
cases components of physical dependency are significantly predominate. The most impressive
part of this phenomenon emerges in those patients who are in a stable medication assisted treatment, meaning in the ideal case are medically healthy, psychologically stable, and socially integrated, but nevertheless after several withdrawal attempts, they are still unsuccessful. The success rate with ANR with this patient segment is correspondingly high!
Using ANR, only the dependency can be treated so that the treatment success is directly associated
with the relevant proportions of dependency or addiction mechanisms in the usage behavior. One
of the goals of the psychological screening is to examine this phenomenon before ANR treatment
and assess it accordingly.
In those cases where psychosocial deficits lead to opioid use or where severe psychosocial deficits have been caused by opioid use, a specialized psychological, psychiatric, and/or social guidance is critical.
Nevertheless, we were surprised to observe that the majority of patients treated did not require
any specific psychosocial follow-up care– actually a logical consequence of the statements above,
but a fact that is difficult for experts from the area of addiction treatment to accept.
For the time being, all ANR treatments as part of the ANR Switzerland pilot project are only taking
place under the supervision of Dr. Waismann.
6.5 Risks and Complications
ANR is a medical procedure performed under anesthesia and therefore not without risks.
This risk can be categorized into four categories as follows based on the potential possible
complications:
1. Risks based on comorbidities
A comprehensive medical history is very important here in order to identify any relevant
illnesses (especially liver, heart, and lung diseases, metabolic disorders, etc.), allergies, or
prior complications from anesthesia (see case study in section 7.5).
2. Risks associated with anesthesia
This risk is similar to that of a routine surgical procedure and pertains to unexpected reactions to medications (e.g., allergies), respiratory dysfunction (e.g., from asthma attacks
or aspiration), heart and circulatory reactions due to prior heart conditions, complications from the placement of the vascular access (e.g., thrombophlebitis, pneumothorax)
as well as other less common dysfunctions (see case study in section 7.5).
3. Complications as part of the ANR treatment
Severe side effects from the ANR treatment are extremely rare. These side effects would
include hypertensive crises, tachycardia or rhythm disorders, development of pulmonary artery hypertension, severe neurological reactions, cramps, gastrointestinal reactions with electrolyte imbalance, aspiration after ending the anesthesia, etc.
4. Psychiatric Complications
Adaptation dysfunctions with depressive reactions, anxiety disorders, temporary feelings of suicide, depersonalization experiences, nightmares, etc.
21
6.6 ANR Schematic
The functional principle of ANR – explained based on a very simplified model.
Fig. 1
Fig. 1: Here the various possible interactions of the agonists (opioid or endorphin) or the antagonists (receptor blockade) on the opioid receptor are illustrated.
Opioid receptors function according to the lock and key principle. Docking the active substance (key) on the receptor (lock) leads to a chemical change in the receptor and has the effect
of an electrical signal in the nerve cells.
Endorphins generally send a psychologically ("normal") signal that can result in either a stimulating (euphoria) or dampening (pain inhibition) effect. Externally provided opioids, on the
other hand, cause a non-physiological ("excess") signal.
Fig. 2:
22
Fig. 2: Receptor blockades are created by so-called antagonists (counterparts). This could be
complete (like with Rapid Detox) or partial (like with ANR). The former refers not necessarily
to an individual receptor, but rather to all the receptors.
Both interaction possibilities for endorphins (a) or the opioids (b) at the receptors is schematically illustrated.
Fig. 3
23
Fig. 3: If the body is now given opioids either in very high doses or very frequently, the opioid
receptors also change with time. It is assumed that the number of receptors as well as their
affinity for opioids increase. If this condition lasts for a certain amount of time, a new
equilibrium is created due to the new receptor constellation, meaning a functionality of the
receptors is adjusted by the opioid supply. The "biochemical dependency" results in the sense
that the opioid receptors are calibrated to "normal" in an overstimulated condition.
Fig. 4
Fig. 4: If the opioid supply drops below a certain level or if the dose is not continually increased,
withdrawal occurs which is triggered by the unoccupied opioid receptors and causes the autonomic nervous system to initiate withdrawal symptoms (sneezing, tear production, tachypnea,
yawning, blood pressure fluctuations, sweating, diarrhea, etc.).
Fig. 5
Fig. 5: The medication receptor blockade triggers an acute withdrawal syndrome that is barely
tolerable for the patient. This is not without danger in view of the massive symptoms of the autonomous nervous system (e.g., pronounced stress response with corresponding stress to the
circulatory system) as well as the pain and cramping.
Fig. 6
Fig. 6: The best-known procedures are the "Rapid Detox" procedures (ROD, UROD, FOEN, etc.).
Using a standardized procedure, the goal is a complete receptor blockade which is likely to
prevent the docking of the opioids (b) which on the other hand also makes an interaction with
the endorphins impossible (a). Because this type of blockade switches off an important component of the endogenous pain and emotional regulation, it is not surprising that the “Rapid Detox”
method almost always achieves unsatisfactory results.
24
Fig. 7
Fig. 7: With the ANR procedure, a differentiated (individually tailored to the patient) dosing of
Naltrexon is used. This occurs with:
- consideration of the history of substance use
- closely monitoring the patient during the ANR procedure under anesthesia.
Fig. 8
25
Fig. 8: Further, an acidification of the metabolism using intravenous administration of ascorbic acid (vitamin C) is used to mobilize and eliminate the largest possible quantity of opioids
stored in the bones and fatty tissues.
Based on previous experience with ANR, it can be postulated that with a differentiated partial
receptor blockade even after a few days an interaction with the body's own endorphins on the
opioid receptors is possible again. However, this requires the most efficient stimulation of the
endorphin system possible from physical activity (including sexual activity), a balanced diet,
emotional and intellectual stimuli, etc.
These three components – the differentiated partial blockade, the mobilization of the opioids,
and the role of the endorphin system – comprise the main distinction from the "Rapid Detox"
procedure!
Fig. 9
Fig. 9: For these reasons, ANR does not actually involve a detoxification, but rather the effective
regulation of the overstimulated opioid receptors with the goal of the fastest possible restoration of normal function to the endorphin system.
If the patient is able to start this endorphin stimulation, the nerve cells and all the associated
regulation systems return to normal condition within a period of days or weeks. This means that
neither the craving for opioids nor the withdrawal symptoms occur.
Fig. 10
26
Fig. 10: it is assumed that in the further course of treatment, meaning as part of the one to oneand-a-half-year consolidation phase with regular oral Naltrexon intake, the blocked opioid receptors dystrophy and thus lose their functionality.
It is worth noting that this process seems to accelerate under the blockade. After a conventional
withdrawal, meaning without a blockade, it can take years until a natural balance of the receptors is achieved. This could be a reason why the addiction mechanism can be reactivated by certain stimuli (smell, environment, etc.) in former addicts, years after successful withdrawal which
can result in a return to drug use.
Fig. 11
Fig. 11: After this time expires no additional blockade is necessary and Naltrexin® can be discontinued.
The statements above are purely exemplary and not (yet) scientifically proven. As a result, this
view reflects the tension between the evidence-based medicine and experience-based medicine.
Practical experience supports this thesis.
27
7. The ANR Switzerland Pilot Project
7.1 Background
After successful treatment of two Swiss patients in Israel, the Spital Interlaken [name of hospital]
stated it would offer ANR treatment under the leadership of the head physician of anesthesia and
intensive care medicine, Dr. med. Patricia Manndorff as a pilot project.
It is worth noting at this point that the cooperation with the Spital Interlaken as an official institution of the cantonal health care services is an important quality criterion for the entire ANR
project. It is a guarantee for patient safety based on a reputable medical background.
In November 2012 the first patients were treated. 26 additional treatment cycles followed, so
that at the time this document was compiled in 2018 a total of 120 patients had been treated.
Notable complications have not occurred or were able to be treated in the intensive care setting.
The results are excellent and exceed those of conventional withdrawal procedures by a promisingly large margin. The pilot project will be continued.
7.2 The Pilot Project in Detail
Formally (legally and scientifically), a pilot project involves an evaluation of "individual healing
attempts", so not a study per se. For the ANR procedure, patients are made aware of various articles in the media and by verbal promotion from patients already treated. Patients were neither
directly recruited nor alerted to ANR by advertising.
The treatment costs were covered by the patients themselves or their families. Before the start
of the project they were primarily supported by abstinence-oriented foundations or other organizations. In the course of the project, a small portion of the treatment costs was covered with an
interest-free loan from a non-profit association in selected cases.
All treated patients gave written permission for treatment and accepted the off-label use of the
substance Naltrexon for this purpose under anesthesia. In addition, they agree that their data may
be used in anonymized form for scientific evaluation.
The following treatment cycles were conducted:
2012 - 9 patients (2 of them in Israel)
2013 - 13 patients
2014 - 28 patients
2015 - 15 patients
2016 - 22 patients (2 of them in Israel)
2017 - 16 patients
2018 – 17 patients
The following patient groups were treated:
• 28 - illegal opioid use (mostly heroin)
• 40 - medication assisted treatment without co-use (15 under diaphin)
28
• 35 - medication assisted treatment with co-use (methadone, buprenorphine, and delayed release morphine)
• 13 - opioid addicted pain patients (morphine, fentanyl, others)
• 4 - others (neither pain nor primary addiction problem)
This is a total of 120 patients, of which 32 were women and 88 men.
It is worth noting that included among these patients were those showing increased risk for complications due to internal co-morbidities (CAD, cachexia, pneumopathy). The willingness to include
such cases was for humanitarian reasons, particularly since at least two of these patients were expected to die prematurely from the existing opioid dependency. Despite the increased risk, there
were never any complications during withdrawal under anesthesia. In two cases, aspiration occurred
hours after the anesthesia. It was treated immediately and was ultimately inconsequential for the
patients.
There has been an encouraging trend in the course of the last two years, namely a significant improvement in the results, which surely can be ascribed to more experience with the treatment in the
hospital as well as in screening and follow-up.
7.3 Results
In accordance with the new Human Research Law (from September 30, 2011, version from January
1, 2014)29, we are not authorized to publish the data we collect. The relatively high hurdle for a scientific study can unfortunately only be managed with great personal and financial effort. As previously mentioned, in terms of legal formality this involves the evaluation of individual healing at- 29
tempts.
In particular, the following criteria for a scientific study are not met:
•
•
•
scientific guidance and evaluation
randomization in comparison with conventional withdrawal methods
review by an ethics committee.
Nevertheless, we are of the opinion that the knowledge gained should not just disappear into a
drawer, and we make the detailed results available for viewing for those who are interested.
The reason:
•
•
•
•
All patients have given their written permission to treatment, and for the use of anonymized
results for scientific purposes.
Every step in the treatment is subject to medical obligation to due diligence.
The results are surprising in that the underlying medical procedure must not be withheld
from anyone in accordance with the legal basis cited in section 3.6. The ANR Switzerland
project fulfills a legal task.
"He who heals is right..."
(quote from a head psychiatric doctor in conclusion to a presentation from ANR)
In the course of the first treatment cycle, the patients were given questionnaires (see attachment) on
which they were to evaluate their condition based on a scale from 0 to 10. In so doing, the following
three parameters were recorded:
29
https://www.admin.ch/opc/de/classified-compilation/20061313/index.html
•
•
•
craving scale (degree of urge for opioids)
psychological well-being
physical well-being.
Scale
Craving Scale
10
9
8
7
6
5
4
3
2
1
0
-1
Before
3 days
3 weeks
3 months
6 months
1 year
Time
Fig. 1 - Immediately after treatment, patients indicated they could hardly sense a craving any more. In the further course of treatment, the value fluctuated between 0 and 1.
30
Scale
Psychological well-being
11
10
9
8
7
6
5
4
3
2
1
0
Before
3 days
3 weeks
3 months
6 months
1 year
Time
Fig. 2 - Likewise, the patients indicated that psychological well-being improved from day to day. The comparison with previous withdrawal attempts played a critical role in this.
Physical well-being
10
9
8
7
Scale
6
5
4
3
2
1
0
Before
3 days
3 weeks
3 months
6 months
1 year
Time
Fig. 3 - After a post-interventional drop, the physical well-being improved visibly. Even here, almost all patients
noticed a significant difference from earlier withdrawal experiences.
These three graphics illustrate very nicely how ANR is different from other withdrawal procedures
(even if it is not statistically significant).
The main difference is in the loss of cravings for almost 95% of patients!
The craving is more or less latently present for several weeks after a conventional withdrawal and
can persist for years in certain circumstances. This would be the main explanation for the high relapse rate after "normal" withdrawals.
Similarly, with ANR the psychological well-being returns to equilibrium more quickly. Certainly the
elimination of the urge plays a key role here; this can be a significant stress factor in a normal withdrawal.
As part of a typical withdrawal, the patient's physical well-being deteriorates for days or even
weeks, and the recovery is quite slow. This has to do in part with the delayed endorphin stimulation.
After ANR, this seems to function more quickly.
The first four years of treating patients as part of the ANR Switzerland pilot project has been an exciting and educational time. The successful treatment of people who had undergone numerous withdrawal attempts and were considered "hopeless cases" is especially noteworthy.
The results presented in the following section were a surprise to most of us:
[As mentioned in section 7.3, we are not permitted to publish detailed results. The legal situation in this
regard needs to be reviewed, however, especially since the results are of interest to the public because
of the legal mission. Therefore, we offer interested individuals or institutions the opportunity to view
detailed, anonymized results.
More information is available at [email protected]]
Of the total of 120 patients treated as of October 2018, 96 completed their treatment within one and
a half years after stopping the consolidating Naltrexon medication.
31
Not all participants were successful, including some patients who ended the treatment unexpectedly
early. On the other hand, some people who seemed to have an uncertain or even poor prognosis were
treated successfully and re-integrated into a "normal" life.
Because follow-up with addiction treatment patients is not very easy, we have defined the following
categories:
XXX - Abstinence goal clearly reached, verified with hair or urine analysis
XX - Abstinence goal probably reached, verified by reliable medical history
X0 - Abstinence goal probably not reached - unreliable medical history
00 - Abstinence goal clearly not reached due to reliable medical history
We assume that this will keep the error rate within limits. Using only results verified by hair and
blood analysis would not be the right way to handle this matter. In this regard, however, it should be
noted that the correlation of the medical history information to the somewhat randomly sampled
hair and urine analysis was 100% (!).
An American study showed that the results of clinical studies do not differ significantly from a simple
evaluation in the practice.30
7.4 Evaluation
The evaluation refers to two time periods:
•
•
the period immediately following the treatment (craving present)
one year after ANR.
An important comment on this distinction: we are always asked about "success rates". To answer this
question, first consider that after the second day of treatment there are factors contributing to the success that no longer have anything to do with ANR. The longer the time since the (initial) treatment, the
more the success is influenced by other parameters (social environment, connection to drug scene, social
integration, relationships, etc.).
Immediately after the treatment, the success is in fact 95%, especially since the craving is practically no longer present and the patients have a solid basis for a drug-free life. Within the pilot project,
one patient used opioids immediately after leaving the hospital, and a second patient did a bit later
with suicidal intent. We have seen again and again that some patients will experiment briefly with
opioids. This is not the result of addiction behavior or even due to a residual dependency, but rather
out of curiosity whether the Naltrexon blockade is actually working...
30
Dijkstra BA, De Jong CA, Wensing M, Krabbe PF, van der Staak CP. Opioid detoxification: from controlled
clinical trial to clinical practice. Am J Addict. 2010 May-Jun;19(3):283-90
32
Of the total of 120 patients treated, at the time of publication of this documentation 104 patients
had undergone treatment one year ago.
Of these 104 patients, 70 were still abstinent after one year which corresponds to a one-year success rate of approximately 67%. Broken down into treatment groups:
•
•
•
•
•
approximately 50% - illegal opioid use
approximately 70% - medication assisted treatment without co-use (13 of 15 with Diaphin!!)
approximately 60% - medication assisted treatment with co-use
approximately 80% - opioid dependent pain patients (one with borderline disorder)
approximately 90% - other
7.5 Comparison with Conventional Withdrawal Procedures
For conventional withdrawal procedures, all things considered, there is no evidence for long-term
success. Only a few studies have examined the success after more than three months and hardly any
study has looked at results after one year.
Author
Source
Year
Time Period
Success Rate
Schirtz et al.
P. Rüesch et al.
Broers B et al.
Hättenschwiler J.
Smyth BP et al.
Genie L Bailey et al.
B. Favrat et al.
Addiction Research BAG
Swiss Arch Neurol Psychiatr
Drug Alcohol Depend
Eur Addict Res
Ir Med J Journal
J Subst Abuse Treat
Drug and Alcohol Dependence
1999
2002
2000
2000
2010
2013
2006
3 months
17%
1 month
18%
1 / 6 months
21% / 28%
1 month
17%
1 month
20%
1 year
10%
3 / 6-12 months 14% / <5%
There is not a single study that has researched the evidence for conventional withdrawal procedures
to show proof of a one-year success rate above 15%. In addition, it is apparent that most surveys
were made on the basis of medical history information (e.g., telephone surveys).
The data situation raises a few questions:
• Is it (still) legal in accordance with the criteria of effectiveness, appropriateness, and costefficiency to invoice conventional withdrawal procedures to insurance funds via a basic service catalog?
• Due to the legal basis (see section 3.6), is there not an urgent need to promote research into
new procedures?
• Is it helpful to expect addicts to undergo a conventional withdrawal as part of such
measures in cases of criminality?
• Does it make sense to send graduates of conventional withdrawals to expensive therapy after the acute phase when the relapse is inevitably over 80%?
33
Evidence based medicine…?
Established addiction treatment medicine claims that ANR lacks evidence as part of a comparable,
randomized study. But where is the evidence for conventional procedures, especially one year
after treatment…?
Although the evaluation of our results in no way satisfies the demand for useful statistics based on
scientific criteria, it does permit the following conclusions:
• ANR is far superior to conventional withdrawal procedures.
• ANR is especially successful for pain patients and substituents without co-use.
• ANR is somewhat less successful for patients with illegal drug use. For these patients, psychosocial care is generally indicated.
34 patients discontinued the treatment. The reasons for this are often not obvious. Using the screenings that were conducted before the treatment, we attempted to analyze the departures:
•
•
•
•
•
•
•
4 loss of contact (considered discontinuation)
11 compliance with taking Naltrexin (ended early, interval too long, etc.)
5 depression, adjustment dysfunction, overstress (opioid as "protective layer")
7 pathological usage behavior (predominance of psychological addiction factors)
3 addiction shifted to cocaine (loss of protective opioid effect)
1 Naltrexin not tolerated (moderate hepatitis)
3 lack of change of environment (lethargy, laziness, etc.)
34
The rate of complications was overall very low. The following events are worth mentioning:
In the first series there was a severe aspiration several hours after the extubation. The cause was
multi-factorial. On the one hand, under anesthesia the patient had already shown signs of withdrawal-related but individually severe elevated gastrointestinal motility with reflux and diarrhea,
while on the other hand the patient required neuroleptics due to his psychiatric comorbidities which
resulted in gastrointestinal dysfunction.
An additional case caused significant problems from undisclosed severe benzodiazepine abuse, with
the result that acute benzodiazepine withdrawal occurred (agitation, hallucinations) on the 4th postintervention day. This required re-admission to the hospital with sedation in the intensive care unit.
7.6 Considerations on the "Scientific Character" of the Results
As mentioned in section 7.3, our studies do not stand up to strict scientific review and must therefore
be interpreted with the appropriate restraint.
Although all participants in the treatment team have become convinced in the course of the last four
years that the ANR procedure would provide evidence based on the strict scientific criteria of effectiveness, appropriateness, and cost-efficiency, our results need to be relativized.
The following factors described in scientific jargon as bias might possibly not be reproducible as part
of a randomized study.
1. The self-financing may possibly be the strongest bias factor with regard to positive results.
On the one hand, we have observed that patients who have been sponsored to a great extent
or even completely tend to end the treatment when they encounter difficulties, such as the
bio-psycho-social adaptation. On the other hand, we have patients who had to carefully save
money for their treatment. These patients generally consider very carefully whether they
really want to end the expensive treatment just because of a temporary discomfort. All patients are notified several times that ending the Naltrexin during the follow-up treatment
phase amounts to a definitive discontinuation and as a result the treatment can no longer be
restarted, especially if opioid use has taken place in the meantime.
2. The individuality of the treatment is decisive for the success of ANR and may be difficult
to reproduce as part of a randomized study. Not only the medication is individual under the
actual treatment in the intensive care unit, but also the type and intensity of the follow-up
35
care is done based on very individual criteria. This means that certain patients hardly require follow-up care and are satisfied with a short phone call every couple of weeks, while
others need intensive psychosocial, and possibly psychiatric or social therapy assisted follow-up care.
3. Although the physician, Dr. Waismann, did not perform any treatments himself in Switzerland and acted “only” as a supervisor, his presence and background with almost 20 years of
experience in the area of addiction treatment medicine had an effect on the patients that cannot be underestimated. Often those who were treated told us that Dr. Waismann had been
able to give them ground-breaking advice for a drug-free life during the course of their treatment. Actually, this is an essential component of any medical activity that probably would not
be entered in the criteria for evidence-based medicine...
7.7 Future Prospects
Because of the excellent results, the project will certainly be continued. In addition to the well-being
of the patients treated, the following objectives are on the agenda:
1. Randomized study
This is imperative per valid practice for the acquisition of the inclusion of ANR in the basic
service catalog for the insurance fund. Even the proponents of established addiction treatment medicine request this study in the name of the scientific community.
As already mentioned, such a study is associated with significant personnel and financial
effort. Additionally, there are ethical considerations for the psychologically and physically
stressful conventional withdrawal treatment that patients are subject to as part of randomization which in certain circumstances have already caused them to fail.
2. Scientific monitoring of pain patients
In view of the excellent results for this group of patients, it might be easier here to set up a
study and use funds from public source (e.g., on the canton level) or from the health insurance and/or accident insurance fund for this purpose. Additionally, the "addiction treatment medicine" aspect plays a rather subordinate role here.
3. Treatment of opioid-addicted newborns
A huge problem31 32 in the USA, it is (still) hardly causing a stir in Switzerland. Nevertheless, 36
this is an emotional topic in which aspects of "addiction treatment medicine" also plays a
subordinate role.
Some of the women treated as part of the pilot program gave birth to opioid-addicted babies. These babies were treated for several weeks or even months with morphine drops.
Except for isolated discrete behavior abnormalities, these children apparently had no additional harm.
31
32
USATODAY.com - Kentucky sees surge in addicted infants. http://usatoday30.usatoday.com/news/health/story/2012-08-26/kentucky-babies-addiction/57331390/1
Deutsches Ärzteblatt, Wednesday, May 2, 2012; USA: Increase in Opioid Dependency in Newborns
http://www.aerzteblatt.de/nachrichten/50044
8. Our experiences after five years of ANR treatments in the Spital Interlaken
The most important insights can be summarized in just a few sentences:
•
•
•
•
ANR is an effective, appropriate, and cost-efficient procedure for treating opioid dependency – regardless of which opioid was used for which reason.
ANR is suitable for all forms of opioid dependency – regardless of the psychosocial background for this dependency.
The results of ANR exceed those of conventional withdrawal procedures by a large margin.
ANR is safe. With an adequate intensive care setting, any possible complications can be
avoided, or intercepted and remedied.
Selecting patients
In retrospect, hardly any selection took place. The biggest hurdle for patients was in financing the
treatment themselves. Because a majority of those who use illegal substances have little money at
their disposal, a (non-medical, socioeconomic) selection took place.
Overall, the number of patients who had to be excluded from treatment for other reasons could be
counted on one hand. In addition to florid psychoses, relevant somatic dysfunctions or severely reduced compliance, unmanageable polypharmacy or consumption of multiple drugs with the risk of
addiction displacement were exclusionary criteria.
In principle, we adopted the position of Dr. Waismann to basically give every patient a chance.
In retrospect, we have successfully treated a few patients for whom we underestimated their prog- 37
nosis.
It is worth noting that there have been no complaints or questioning of the methods by any patient
with a negative result (i.e., after abandoning the treatment).
Anecdote: Not "disappeared", but freshly shaven!
A well-to-do woman who lived on the northern shore of Lake Geneva requested that we treat her son. He was
homeless, living in the streets of Lausanne, and using heroin daily. Correspondingly, his appearance was imposing: uncombed, shoulder-length hair, a wild beard, and extremely unpleasant body odor. He had apparently
undergone his own withdrawal attempt a few years prior with illegal methadone and as a result had to be
resuscitated and placed on ventilation. As a result, he had not attempted to stop his drug abuse for years. After
the ANR treatment, we wanted to visit his hospital room with a physician while making hospital rounds, but it
seemed that the patient had disappeared. We inquired with the nurse and found out that he was very likely in
the room – he had spent about an hour in the bathroom. We simply could no longer recognize him after he
spent an hour in the shower, cut his hair, and shaved his beard. Today he is employed again as an electrical
engineer. His mother still talks about a miracle to this day...
Prognostic considerations
For one thing, with increasing experience we were rather in a position to estimate the prognosis as
part of the prior discussions, and then again, we were rarely mistaken – in both directions. Patients
with the best prerequisites, stable environment, adequate daily structure, steadfast motivation, and
sufficient distance from the drug scene have terminated the treatment, some of them for unknown
reasons. Others from unstable relationships, with significant psychosocial comorbidities or even using multiple drugs were successfully treated over the long-term, to the surprise of all involved.
Correspondingly, the prognostic considerations listed below are to be taken with caution.
Factors beneficial to the prognosis
Initially it was our opinion that an important distinction between dependency and addiction behavior had already been adopted. The higher the share of (somatic) dependency and the smaller the
influence of any (psychological) addiction, the higher the probability of successful and sustainable
treatment.
As a model case of a prognostically beneficial initial situation, we see patients in a stable but somewhat
heavily dosed medication assisted treatment who live in a sustainable environment with regulated daily
structure and have professional prospects.
Additional prognostically beneficial factors are:
- detrimental side effects from medication assisted treatment
- independent financing for ANR treatment
- no co-use, and sufficient distance from the drug scene as a result
- regaining driving privileges after drug-related revocation of driver's license as a goal
- responsibility as a parent
- abstinent partner
- support from the family that is not felt as pressure
- opioid dependency due to pain problems.
Anecdote: One withdrawal attempt per year...
The almost 35-year-old man had been in a heroin program for about ten years after several failed attempts
with methadone substitution. About once a year he underwent a withdrawal attempt, but always failed with a
massive craving which was still there months after the withdrawal. For about two years, he was also unable to
work due to a depressive disorder. After the ANR treatment, he recovered well enough to be able to participate
in sports again and thus gradually stop taking antidepressants. Today he is working full time again as a foreman
and a year and a half after the ANR treatment he had regained his driver's license again.
38
Factors not beneficial to the prognosis
Complementary to the model case for a prognostically beneficial situation, constellations that are
characterized by unstable family relationships, persistent contact with the drug scene, lack of daily
structure, and pathological usage behavior frequently result in treatment termination. From a psychiatric point of view, it has been shown that patients with ADHD problems and those with narcissistic
personality traits have a poorer prognosis.
It is particularly worth noting that patients who do not have to pay for the treatment themselves terminated the treatment somewhat more frequently than those who had to pay for it themselves or
had their family pay. An interesting observation is that patients who did not adhere to the smoking
ban in the hotel terminated the treatment more frequently than those who did not smoke cigarettes
in the hotel room.
An additional, more negative factor is excessive motivational pressure from parents or other proponents of the patient's family system. Affected parents, siblings, or partners represent a certain comorbidity for their dependent relative from a systemic point of view after years or decades which often
still persists for a long time despite successful ANR treatment of the index patient and can have a
correspondingly counterproductive effect. Oftentimes mistrust plays a significant role, especially if
the patients have often lied to or even stolen from those close to them as part of their dependency. In
addition, if there were regular assurances in the past regarding a sincere will to abstain from taking
drugs, that generally vanished in to thin air when the urge for opioids was too strong.
From a systemic view, it is extremely important that this fact be given the necessary attention. It can
be important and helpful for the affected relatives, even healing, when they are made aware that their
child's or partner's opioid dependency is not a psychosocial problem or character flaw, but rather a
reversible disorder of the brain function.
39
It corresponds with a frequent observation that parents who have been through a lot with their drugaddicted children remain extremely skeptical and mistrustful even long after successful treatment.
Anecdote: Treatment – or Eviction
It seemed like the young man's parents had to drag him in to the first meeting. They had come across the ANR
procedure while researching on the internet and had confronted their son with it. It was soon apparent that he
had little of his own motivation. In retrospect, it came to light that they had apparently given him an ultimatum:
either he would undergo treatment, or they would evict him from their home within a week. The situation was
made more difficult by the fact that the patient had used drugs of all types since early childhood and as a result
displayed impaired emotional regulation and had acquired a differentiated knowledge on the effect of drugs.
Surprisingly, he was able to stop using opioids altogether, but switched to cocaine which required hospital
inpatient follow-up care. He continues to refrain from using heroin to this day.
Additional prognostically adverse or negative predictive factors:
- lack of change of environment, lack of daily structure
- multiple drug consumption (including benzodiazepine, cocaine, and alcohol)
- external motivational pressure
- sponsored patients or financially stable patients
- unwilling to reduce opioid dose before the ANR treatment
- excessive use right before ANR treatment.
Anecdote: Only a matter of time
Mr. A came calling again and again although he was unable to pay for the ANR treatment on his own. It just so
happened that a successfully treated businessman wanted to show his gratitude by covering the cost of treatment for another patient. Mr. A arrived at the hospital totally "loaded", particularly since he had not considered
it necessary to reduce his opioid dose before the treatment. Although his motivation for a drug-free life had
always seemed sincere, in the weeks before the treatment he had been using excessive amounts of drugs, primarily benzodiazepines. In addition, he refused the change of environment urgently recommended by the
treatment team. This meant that after the treatment his dealer was at his front door almost every day, offering
him drugs. The termination of treatment was really just a matter of time.
The problem with using multiple drugs
Multiple substance use is frequently characterized by taking drugs from various substance groups.
This generally shows the characteristics of a dependency.
According to the WHO lexicon for alcohol and drugs, polytoxicomania means the "use of more than
one type of drug by an individual, both at the same time as well as one after the other, with the intent of
accelerating, multiplying, or counteracting the effects of other drugs."
Polytoxicomania is differentiated from multiple substance dependency in that no urgent dependency
on a certain substance group must be present with polytoxicomania. Based on our experience, there
is often an opioid dependency as the focus of the substance abuse, and very often a rather highly
dosed medication assisted treatment.
The use of multiple drugs exhibits two aspects which could provide at least a partial explanation for
such behavior:
•
On the one hand, years of opioid use leads to a depletion of the mental experience and the
"normal" emotional fluctuations (feelings of happiness and sadness), leaving the addict feeling emotionally "level" and missing the "flash", or the drug-imparted moment of happiness.
In this situation, other (non-opioid) substances can create such a "flash" for brief moments.
•
On the other hand, with high dosage medication assisted treatment there is very often an urge
for opioids and/or other substances. In these cases, co-use (e.g., of heroin by the medication
assisted patient) or taking other substances can suit the purpose of suppressing this urge.
The most frequently used substances (with increasing importance) are:
- benzodiazepine flunitrazepam (Rohypnol®) and midazolam (Dormicum®)
- cocaine, especially cocaine base (crack cocaine)
- alcohol
- party drugs, amphetamines
- cannabis
40
Benzodiazepine
This substance group is right at the top of our "worry barometer", particularly since the problems it
causes can far exceed those caused by the opioids, and for the following reasons:
•
•
•
•
Benzodiazepine use and the extent of that use is often not disclosed or whitewashed over
("now and then to fall asleep...", etc.).
Patients who have used high doses of benzodiazepine for long periods of time often display
one or more serious personality disorders, compliance is impaired, and the ability to enter
into agreements is restricted.
In the adaptation phase after the ANR treatment, when the patient still shows impaired vigilance and limited physical well-being, there is the threat of switching to the use of benzodiazepine, most likely due to its paradoxical stimulating effect.
Whenever possible, opioid addicts using multiple drugs should undergo benzodiazepine
withdrawal before the ANR treatment. Such a withdrawal is significantly more difficult after
the treatment.
Despite the problems listed above, most of the patients treated as part of the ANR pilot project were
successfully able to avoid this type of addiction transfer. However, most of these patients required
an in-patient setting.
Cocaine
Cocaine is often used together with heroin as a "cocktail". In so doing, the stimulating effect of the
cocaine compensates for the somewhat dampening effect of the heroin or the opioid, which is used
41
to compensate for the very energizing effect of the cocaine.
A very important insight from our work is the fact that opioids exert a type of protective effect against
other substances. This means that this protective effect is gone after the ANR treatment. This circumstance, at least in the case of three patients treated as part of the ANR pilot project, resulted in the
termination of treatment. All three used cocaine during the ANR treatment, which in turn led to the
emergence of a stimulating effect so pronounced that they could not sleep for several nights. Out of
desperation, they ended the Naltrexin® treatment in order to "come down" with the help of opioids.
We discourage patients who indicate to us that they are thinking of still using cocaine from undergoing the ANR treatment. As with the benzodiazepines, a withdrawal from the cocaine is also indicated
here. This is also significantly easier to do before the ANR treatment than it is after.
At this point it is worth mentioning that there is no treatment for treating excessive use of cocaine or
crack cocaine. In terms of a (de facto experimental) treatment attempt, ANR can be used in the following way:
•
•
gradual replacement of cocaine with opioids, possibly supplemented with Ritalin® and/or
an anti-depressant such as duloxetin (Cymbalta®)
after a stabilizing phase, the opioid withdrawal is done with ANR.
Alcohol
Patients with excessive alcohol consumption (more than three units daily) are not permitted to undergo ANR treatment. The risk of alcohol withdrawal syndrome or delirium would be too great.
Interestingly, a transfer to using alcohol is observed less often than expected. To the contrary, there
were patients who used alcohol regularly but after the ANR treatment the desire was significantly
reduced or even altogether gone.
Two mechanisms could play a role here:
•
•
On the one hand, the opioids have a certain protective effect against the effect of the alcohol
such that the patients often indicate they would have difficulty tolerating alcoholic drinks.
In addition, the effect of the Naltrexon (Naltrexin®), which can be used to consolidate the
alcohol abstinence, certainly plays a significant role.
Party drugs, amphetamines
We almost never observed a transfer of use to these types of substances. However, there were patients who used such drugs for years and did not want to avoid them after the ANR treatment. We
consider these substance classes to be less problematic although here (with the amphetamines more
than with the party drugs) the elimination of the protective opioid effect can play a role.
Cannabis
Like the substances described above, cannabinoids play a rather subordinate role. Opioid addicts 42
who smoked marijuana regularly before the treatment rarely give it up after the treatment. In individual cases, we observed that even here the tolerability after ANR treatment generally decreased
somewhat.
The protective effect of the opioids with regard to psychotic illnesses is known and well-documented.
Theoretically, the use of cannabis by vulnerable personalities after the elimination of opioids could
also result in increased disorders in the form of the psychoses. We were unable to observe such processes as part of the previous treatments.
Adjustment disorders
We previously discussed a protective effect from opioids several times. Of course, this also has an effect on the psychological level. Patients in medication assisted treatment in particular indicate that
they feel like they are "wrapped in cotton", which is generally seen as positive and helpful for coping
with everyday life.
The main problem from ANR treatment - the speed - manifests itself here. Patients awake from anesthesia and find themselves in an entirely new situation. The perception of the own person and the
environment is completely changed in some cases. In addition to the positive aspects (more intense
perception of smells and colors), this can also cause problems on the psychological level in that
stresses, self-criticism, conflicts, etc., are perceived much more intensely. We often make the observation that the patients respond much more emotionally in the days following the treatment and are
often brought to tears at the slightest provocation.
In the early adaptation phase, these surges can be very pronounced. Occasionally the situation is expressed as a manifest depressive episode or even in the form of a suicidal crisis. On the one hand,
these processes must not be overvalued, but at the same time they require close observation especially since a serious adaptation disorder could develop under certain circumstances.
Anecdote: Disastrous "old remedy"
The patient showed the best prerequisites for ANR treatment and we assessed the prognosis as very good. After
the treatment a depressive disorder set in, however, it seemed to gradually subside. After this, things were
going so well for the patient that he decided to take a big step professionally. This unfortunately led to an overload situation which had a secondary, negative effect on his family life. The grip of the "old remedy" seemed
unavoidable to him, especially since he had always felt "shielded" and safe on methadone.
The more a patient is able to lead an "endorphin-rich" life, meaning to bring about a balance with
movement, sports, sexual activity, and intellectual stimulation, the faster the psychological stabilization sets in. Conversely, a lack of natural endorphin stimulation leads to a manifest depressive disorder.
Unfortunately, in such situations the "proven remedy" is reached for, meaning Naltrexin® is ended
and generally a strong dose of opioids (usually methadone) is taken to self-medicate. In all cases, this
is a termination of treatment. Oftentimes the patients then try to start the Naltrexin treatment again,
which can result in more or less severe withdrawal symptoms depending on the opioid quantity consumed.
Compliance
In medicine, there is talk of patient compliance as an umbrella term for the patient's cooperative behavior as part of a therapy. This can involve simple, one-time actions as well as longer-term processes
like permanently taking a medication.
The term can also be expressed as treatment adherence. Good compliance means consistently following the medical advice. According to the World Health Organization (WHO)33, only 50% of patients on average have good compliance. In many areas of treatment for chronic diseases, after one
year only about 50% of patients follow the initial treatment plan.
The guidance of opioid addicted drug users – in particular those who frequented delivery points for
longer periods of time – presents additional challenges in terms of compliance. Oftentimes these patients are very smooth customers regarding substance abuse, in some situations have "pharmaceutical experiments" in their background, and often feel superior to the medical staff. If this situation is
not discussed quite explicitly, the outcome of any experiment is predetermined.
It is especially important to convey the significance of regular Naltrexon intake to consolidate the
receptor blockade after the ANR blockade.
Compliance prior to the ANR treatment
33
http://www.who.int/chp/knowledge/publications/adherence_Section1.pdf
43
This is generally already apparent at the first meeting and initial clarification. Missed appointments,
tardiness, and vague medical history information can be an indication of impaired compliance and
already provides an early statement on the prognosis.
The intentional non-disclosure of important medical facts, possibly out of fear of not being permitted
to undergo the treatment, is understandable in individual cases. However, during the treatment it
can result in significant and even potentially dangerous situations. An example would be not disclosing epilepsy or indicating amounts of benzodiazepine that are much lower than what is actually used.
The latter leads to massive withdrawal syndrome with hallucinations and protracted need for IPS.
The drug excesses or missing dosage reductions are already indications of impaired compliance even
before the treatment which can manifest as early termination of treatment after the treatment.
Compliance after the ANR treatment
Immediately after the sedation, all patients need closely coordinated support, generally in the form
of bedside observation. After the anesthesia is ended, they are physically exhausted and are psychologically between dream and reality. Later, they need help to go to the toilet and with eating and
drinking. The significance of personal encouragement should not be underestimated here.
In the course of the first two to three days, it is very important to strive for the most natural "steady
state" possible, meaning avoiding pharmaceutical intervention whenever possible. The gastrointestinal side effects (including diarrhea, occasional cramping) disappear spontaneously, or the more
quickly the patient can be motivated to ingest food.
What is generally known as "withdrawal" corresponds with what medical nomenclature calls a syn44
drome, meaning a collection of various individual symptoms. These could be:
- restlessness
- stomach cramps, diarrhea
- restless legs, cramping
- insomnia
- aching limbs
- etc.
The essence of these symptoms results from "true" opioid withdrawal in an immense urge for the
substance and the barely controllable intention to immediately obtain and take opioids in order to
end this intolerable condition.
After the treatment some of these symptoms can occur for a few days with greater or lesser strength.
However, if the last step is omitted from the start, then the urge is not part of the symptoms! It is
important here to make clear to the patient being treated that their symptoms are not part of withdrawal syndrome, but rather a consequence of the treatment. This is generally successful in the
course of treatment because after the third day these phenomena abate and do not become worse
with continued opioid abstinence (as the patient might expect from previous withdrawals).
The post-interventional sleep disorders which occur require special mention especially as they can
be really persistent and drag on for several days. In terms of experience, sleep deprivation also
tempts patients to make their own pharmacological experiments.
The following two principles must be conveyed here:
•
During the treatment, the patients received very high doses of sedatives and narcotics. These
alone can disrupt the day/night cycle for a few days.
•
The best sleeping aid is an active (endorphin-rich) day. This means that the patients are not
tired during the day because they have slept so little during the night, but rather they cannot
sleep because they were too inactive during the day.
Especially in the development phase after the post-interventional adaptation, it is particularly important to motivate the patients to be active – ideally even in sports activities. When they experience
this second, important principle in their own body, it is generally unnecessary to pursue additional
activities as part of the follow-up care. From this perspective, we also encourage patients to not stay
away from work for too long and to return as quickly as possible to a normal daily routine.
As already mentioned above, taking Naltrexin® is of critical importance after the treatment. In the
early post-interventional phase, a massive craving inevitably starts after ending the Naltrexin; this is
usually followed by a return to opioid use. Ending the Naltrexin prematurely at a later point in the
follow-up treatment is less dramatic but manifests itself with a subconscious urge for the substance.
This can mean that subconscious locations are frequented, or people are contacted who are associated with the past drug use. Usually the affected person realizes this too late.
After a conventional withdrawal, it could take five to ten years until the natural balance of the opioid
receptor system is established once again. One of the reasons for this could be that former addicts
who have lived drug-free for more than five years could relapse again under certain circumstances.
Here it appears that the subconscious mechanisms play a role.
After the ANR treatment, this process is accelerated. It is assumed that the impaired receptor situation normalizes quickly under the medication blockade.
45
Anecdote: No more craving
Mr. E. already had contact with many kinds of consciousness-changing substances during his years in school.
His drug use history ultimately ended at Platzspitz Park and Letten train station. After leaving the open drug
scene he entered withdrawal treatment, followed by successful addiction treatment including vocational training. After about five years of living drug-free, he came into contact with heroin at a party when someone literally
put it right under his nose. This triggered a cascade in his autonomous nervous system with damp hands and a
running nose, and he developed an uncontrollable "urge" for the substance in his head. After a period of returning to intense use, he came to the newly opened heroin dispensary. One year later he traveled to Israel and
was treated there with ANR and freed of his dependency. In order to unregister from the dispensary, he entered
the facility with a great deal of concern that it could re-trigger a negative spiral – but nothing happened! Neither
the smell nor the familiar faces in the heroin dispensary triggered even the slightest urge...
Comorbidities
In the interest of patient safety, a complete medical history is extremely important for the treatment
team. For those comorbidities that are associated with increased treatment risk or even justify exclusion from treatment, it is imperative that they be recorded and evaluated. Here the approach of a
three-specialty team (general internal medicine, anesthesia/intensive care, and psychiatry), enhanced by the information from the primary care physician, has proven to be extremely helpful.
Somatic comorbidities
A detailed interview with system, patient, and family medical history, a review of any existing physician and hospital reports, as well as a phone call to the primary care physician are helpful here.
46
Relevant disorders are:
- coronary and hypertensive heart disease, depending on the severity of possible exclusionary
criteria
- neurological conditions, epilepsy
- pulmonary disorders with impaired gas exchange
- severe liver or kidney function disorders
- pregnancy
- allergies
- complications from anesthesia in the past
- florid infections.
Psychiatric comorbidities
For the psychiatric disorders, basically the need for treatment, the current course of treatment, and
the stability of the medication treatment are crucial to the decision to exclude a patient from treatment. Patients with a florid or insufficiently adjusted psychosis or affective disorder are not treated.
Similarly, suicidal patients or those with significant cognitive deficits are excluded from treatment.
Opioid addicted pain patients
This sub-group is extremely diverse; the patients often have a very long and complex medical history.
Almost always, these patients have had a predominantly local problem with pain explainable from
the medical history (trauma, surgery, biomechanics, etc.) that is explained as "pain disorder". At some
point opioids were relied on in conjunction with this pain disorder. It should be noted at this point
that prescription of opioids from the doctor providing treatment was in most cases an act of desperation when there were no other options in sight. In our opinion, there were only isolated cases where
the opioids were given somewhat too frivolously, or the dosage increase was done too quickly.
Our experience with opioid dependent pain patients shows that the statement that opioids
would not create a dependency if they are used for treating pain is not true!
Special mention is made of opioid-induced hyperalgesia – a phenomenon that is known in pain
therapy and for which the incidence and significance is apparently underestimated. This involves a
hypersensitivity to pain that on the one hand is probably caused by increasing the dosage of the opioid analgesic and on the other hand increases at the same time as the dosage increases. This phenomenon is the cause for the situation in which the patients complained about increasingly stronger
pain despite the highest dose of opioid analgesics and also exhibit a significant topographical extension of the pain zone(s). These areas are also characterized by a measurable hypersensitivity to mechanical stimulation (touch, pressure, manipulation, etc.).
Anecdote:
Anecdote: Resolving the other symptoms
A patient with chronic back problems for which no organic entity could be verified despite a variety of evaluations showed a type of pronounced touch sensitivity that she stated prevented her from even tolerating wearing jeans and "normal" clothes. At the consultations, after a few minutes she had to stand up, lay down, or walk
around which created a certain lack of understanding at some examinations. After the ANR treatment, these
problems disappeared within a few weeks and the patient was able to start medical training therapy again and
thus come to grips with the remaining symptoms.
These and similar developments surprise us again and again. To put it somewhat simply, the pain
generally disappears with the opioids. The patients re-learn how to treat symptoms with their body's
"own pharmacy", i.e., via endorphin stimulation.
Of the ten opioid-addicted pain patients treated as part of the ANR pilot project, there was only one
case of a resumption of opioid treatment; in this case under dramatic circumstances and in the midst
of a highly complex psychosocial stress situation. At any rate, the patient was able to use a significantly less potent preparation at a lower dose.
47
9. Appendix
Appendix
9.1
9.2
9.3
9.4
Interview with Dr. Waismann
About Dr. Waismann
Feedback from patients
Helpful metaphors
48
9.1 Interview with Dr. Waismann
interviewed by Dr. med. Daniel Beutler
February 2012 in Ashkelon, Israel
What is the basis for ANR?
The most important basis is the knowledge that
opioid dependency involves an organic brain
disorder, meaning it is structurally caused and
not primarily a psychological phenomenon.
Regularly taking opioids over longer periods of
time results in graphic changes on the level of
the opioid receptors in the brain. It is assumed
here that these receptors increase in number
and affinity and so get into a state of stimulation, which in turn creates a craving, an irrepressible urge for opioids. The goal of ANR is to
use medication to remove this state of stimulation.
What exactly takes place in an ANR treatment?
The main element of the treatment is a medicated, or chemical blockade of the opioid receptors in the brain with the help of what are
known as opioid antagonists. However, since
such a blockade is acute and, in most cases,
would trigger very severe withdrawal symptoms, patients are put under anesthesia for a
short time. As a result, unlike conventional
withdrawal treatments, the symptoms are
made tolerable for the patients. After they
awake from the anesthetic, the opioid dependency is temporarily blocked and with time entirely alleviated.
How does that work in practice?
After detailed pre-evaluations, the patients enter the clinic and spend half a day in preparation for the treatment. This is done with sedating and circulation-stabilizing medications
with the goal of muting the withdrawal symptoms somewhat under anesthesia. In addition,
in this phase the opioids remaining in the body
are flushed out of the fatty tissues and bones
with acidification of the metabolism using
ascorbic acid. Further, a vascular access device
and a gastric tube are placed, and the patient is
intubated but muscle relaxant is not administered so that they will breathe independently
while under anesthesia.
What motivated you to work with addiction
disorders?
As a medical officer in the Israeli army, I was
confronted with wounded soldiers who would
be left with a dependency on opioid pain medications after years of pain therapy. Some of
them were close colleagues of mine who languished like drug addicts even though they
were not prone to addiction either psychologically or in terms of their character.
Can you explain how you came about these
methods?
I did intensive research of the medical literature in order to learn as much as possible about
how opioids are metabolized in the brain. I was
quickly convinced that a brain function disorder on the level of the receptors had to be responsible for the dependency. I later found out
that some addiction experts in the 1980's had
already experimented with medicinal withdrawal procedures and had more or less successfully applied the concept of the receptor
blockade under anesthesia. These researchers
were almost exclusively psychiatrists and psychologists. As a specialist in intensive care, I
have further developed the methods on this
level.
How often have you already used your
methods?
One of my first successfully treated patients
was a child who had received high doses of
morphine due to a brain tumor and as a result
ended up with such a severe dependency that
no communication whatsoever was possible
with the environment. In the meantime, I have
treated a few thousand patients, including
many prominent figures from politics, business, and show business. This significant success does not mean that I am some kind of miracle healer, but rather justifies my deep conviction that opioid addicted people don't need anything other than treatment based on modern
medical criteria.
This means the outline of the method has
already been known for more than 20
years. Why was it not generally accepted
for so long?
There are several reasons for this. The psychiatrists and psychologists mentioned above
have generally used the procedure in their own
practices and as a result incurred significant
risks. They were not equipped to deal with
complications from the anesthesia, especially
as they did not have the necessary intensive
care equipment available. This lead to quite a
few complications with lethal consequences
which were critically assessed by the experts.
This in turn caused the method known as
"rapid detoxification" to be evaluated as dangerous and therefore not recommended by the
Ministry of Health for many countries.
What differentiates the method developed
by you from other procedures?
An important factor is the individuality of the
patients. A young man, who only recently used
heroin but no additional substances
is very different from a patient who has been
taking high doses of opioids for years due to
chronic pain. This fact requires careful evaluation before the treatment, not least to estimate
the risk of the anesthesia. Lastly, I care for each
patient personally with my well-coordinated
team. I can apply all of my experience and offer
the patients individual treatment. "Rapid detoxification" was used by many doctors almost
like a cookbook – that is not possible with ANR.
Additional differences from what is called
the "turbo withdrawal" or "rapid detox"?
At the start of my practical activity in this area, 50
I used the "rapid procedure" myself or procedures from the "complete receptor blockade".
But one day I had to realize that many patients
were not doing well after the treatment and
they often relapsed although the receptors
were verifiably blocked. Soon enough I arrived
at the realization that with the treatment, the
endogenous opioid system (via the endorphins) and therefore an important part of the
physiological regulation of the neurotransmitters had been damaged. This meant that the receptor blockade had indeed dampened the urge
for opioids, but on the other hand the patients
also went through a kind of "chemical depression". Because I paid special attention to this
circumstance, I described my treatment
method as "regulation".
How do you solve the problem with the
safety?
For me, the medicinal opioid withdrawal
clearly belongs in the hands of the experts.
Those who specialize in administering opioids
and controlling with effect minimizing substances, i.e., to antagonize? The anesthesiologist or the intensive care physician! For this
reason, ANR clearly belongs in the hands of an
experienced team and in the intensive care unit
with access to a public hospital. I can say with
good conscience that during my treatments I
have not recorded a single serious complication or even a fatality.
Are there additional reasons why the
method has yet to become established?
An ideological aberration! Still today the principle is held that all forms of drug dependency
are primarily a psychological or psychosocial
problem. The person dependent is stigmatized
by this because it is assumed they must have
mental weakness or a difficult back story in
substance dependency. This may apply in some
cases, but certainly not for the majority of patients who possibly experimented with drugs
or took drugs because of a temporary personal
crisis.
That is a bold statement.
No. I am convinced that opioid dependency is
primarily an organic brain problem – regardless of which reasons make a person use opioids and which psychosocial consequences resulted from the dependency! It is a fact that an
army of psychiatrists and psychologists live on
this incorrect approach. The modest success
rate for this type of treatment speaks for itself...
This assertion will probably start a few discussions...
Talk to the patients I have treated. But don't try
to convince a psychiatrist about ANR – in my
opinion outdated psychosocial concepts are
too deeply rooted and all notable addiction experts are unfortunately almost all psychiatrists,
even in Switzerland. Certainly, these addiction
experts have justification in the psychosocial
initial and follow-up care of the patients
treated with ANR. This should also be promoted.
How does this work with the dependency
on pain relievers?
In the past, pain was considered a symptom
and treated accordingly. Today (especially in
the US), pain clinics are sprouting up all over
and calling pain a chronic disease. This creates
enormous expectations on the part of the patients, and when all the pain-modulating treatments don't help, opioids are used; they are always effective, even from a certain dose (often
a very high one for chronic pain). A fatal devel- 51
opment which has given countless people an
opioid addiction! The withdrawal treatment
using ANR is not any different than those used
for illegal drug addiction.
How do you assess medication assisted
treatment?
In view of the scientific knowledge that the sustained intake of opioids leads to structural
changes and to an increased in the (overstimulated) receptors in the brain, this is a medical
catastrophe a million times over! Heroin has
been around for about 100 years, methadone
for 70 years: would you let yourself be treated
in a hospital with such outdated methods?
There are hardly any studies of ANR. Why
is that?
The patients are evaluated after the ANR procedure for symptoms of withdrawal. The methods can only be refined so that the withdrawal
symptoms simply disappear after a certain period of time. Did it take studies to show that the
appendix is no longer present when you have
had it surgically removed? I am asked time and
time again about long term results; that is no
longer my area. I alleviate opioid dependency –
what the people then make of it is another thing
altogether. Bottom line, the ANR treatment is
based much more on experience than on theories. Nevertheless, this is more than simple experience-based medicine.
What if a university were to grant you a research contract?
This has already been offered to me by a university in Texas. Scientific monitoring, i.e., with
brain scans, that would have examined exactly
what happens in the brain structures with the
opioid receptors would of course be of great interest to me. Because I would have had to stay
in the USA for a longer period of time, I had to
decline in consideration of my family. Honestly,
I have already regretted this decision...
Dr. Waismann at the patient's bedside, together with
Dr. med. Patricia Manndorff, head physician FMI
It would be interesting to know how the patients are doing after the ANR treatment.
There are drug addicts who suffer from more
or less pronounced psychosocial deficits after
years of drug abuse. My experience shows that
those persons for whom opioid dependency
could be relieved with ANR had much better
starting conditions for a drug-free life and
could get back on their feet much more quickly
than if they would have had to fight back
against the craving despite the withdrawal
therapy. Nevertheless, I have to reiterate this
part does not fall under my area of responsibility.
Additional reasons?
Neither the receptor blockade nor the anesthesia procedure and the follow-up care take place
according to a schedule. In particular, the dosing is a key component of neuro-regulation. I
sort of "play" with the depth of the anesthesia
and try to keep it on the most level plateau possible so that I can evaluate the reactions of the
patients. Something like this cannot be standardized. Therefore, I don't submit any written
guidelines when I forward my method to someone, but rather I only do "bedside teaching",
meaning I pass on all of my personal knowledge
and experience one-to-one. The numerous
studies on the (reputably conducted) "rapid detox" procedure can be consulted as a scientific
basis.
How were you able to have your method
accredited in Israel?
The accreditation was done after several personal discussions with the Department of
Health. Today I am the medical director of a
clinic that is affiliated with a public hospital. 52
Further, the treatments for opioid-addicted
disabled veterans is paid for by the Department
of Defense. However, the official addiction
medicine still refuses to acknowledge my
method.
In other countries, as in Switzerland, I have
been more successful in speaking with skeptics
in person and sometimes even convincing
them. The best references, though, are those
who have been treated. This includes more
than a few who were written off as hopeless
cases...
What has your experience been in Switzerland at Spital Interlaken?
In the beginning there was a great deal of skepticism. But after the first successful treatments,
which gave way to enthusiasm to understand
and master the ANR procedure in all of its facets. The team at Interlaken is outstanding and
the infrastructure is excellent. The types of patients are quite demanding, especially as most
have been in medication assisted treatments
for several years where there are rules that are
contrary to the abstinence-oriented philosophy
of ANR. The threshold is too low for a return to
the substitute medication as soon as the everyday difficulties occur. In addition, interested
patients are very often confronted with the
clearly dismissive attitude of the doctor who is
treating them (usually a psychiatrist). Of
course, this often occurs out of ignorance. After
three years of ANR treatments in Switzerland,
a certain amount of resistance has disappeared.
53
9.2 About Dr. Waismann
"I am not a genius – just a doctor who is tired
of seeing heroin addicts being tossed onto the
sideline or fed methadone to keep them under
control..."
"In the last 50 years, nothing has changed
with regard to treating opioid dependency,
because it was taken out of mainstream medicine..."
These quotes reflect Dr. Waismann's attitude toward opioid dependency and his vision on how to
treat it. On the one hand, he is convinced that this is a reversible organic problem in the brain, not
primarily a psychological or psychosocial problem. On the other hand, he advocates forwarding
the withdrawal treatment he developed to third parties as "good medical practice".
Born to a diplomatic family in Brazil, Waismann emigrated to Israel at the age of 24, studied medicine, and specialized in surgery and intensive care medicine. He completed his military service
with the Israeli infantry, finishing his service as commanding medical officer (colonel) of an antiterror unit.
As an army doctor, he was confronted with the consequences of repeatedly administering opioids
to severely injured patients in the acute phase or later during their rehabilitation. He saw highly
decorated soldiers, some of them his close friends, become addicts after prolonged treatment with
opioids, regardless of their psychosocial background or their character. After discharge from the
clinics, they were more or less harshly denied further administration of opioids with the result
that more than a few landed on the streets and got by with illegal drugs. Further, as an intensive
care physician in the neonatal unit, Waismann guided the withdrawal treatment for babies of heroin-addicted mothers. Affected by the difficulties of these painful opioid withdrawals, he started
to spend a great deal of time studying this issue.
From the very start, his focus was not on the psychosocial backgrounds of the persons dependent,
but rather on the research into the suspected organic brain mechanisms. He searched for the common denominator for dependency in babies born addicted, street junkies, and opioid addicted
military veterans. In the process he became convinced that all three suffer from the same organic
brain disorder and therefore needed the appropriate medicinal, not primarily psychiatric, treatment!
Based on the experiences with the "rapid detox" procedure, he experimented with the substance
Naltrexon and soon noted that the "mechanical" approach of a complete receptor blockade actually seemed possible but was not expedient in practice especially since patients did not fare well
after such treatments. It was groundbreaking for today's ANR procedure to realize that a young
person who has used heroin for a couple of months cannot be treated the same way as someone
who has been receiving medication assisted treatment for years with high doses of methadone or
buprenorphine. The history of the addiction came to have great significance – not to define an
"addictive personality", but instead to estimate the extent of changes to the structure of the opioid
receptors. Today's ANR treatment – the accelerated regulation of the brain structures of the
54
endogenous opioid system that is responsible for the dependency – is the result of these experiments and the experience from another twenty years of treating those dependent on opioids.
The motivation depicted above from the personal and biographical background, the persistence
and pioneering spirit of the Israeli doctor and scientist, Dr. Waismann, is the reason a method is
available today that facilitates a paradigm change in addiction medicine for rethinking the therapeutic approach and giving addicts the opportunity to receive sustainable treatment with a chance
to live a substance-free life.
Waismann's opinion of the medication assisted treatments is that they are not actually treating
the addicts, but instead are more to "reassure society" with the goal of reducing drug-related
crime and preventing an open drug scene like that in Zurich and Bern in the end of the 1990's. To
the argument of "harm reduction" he counters that it is much more a matter of reducing harm to
society than provide the addicts with a treatment based on the principles of modern medicine.
Today his main interest is in passing on his knowledge and experience with ANR. He has trained
anesthesiologists around the world in university clinics and public hospitals, including in Switzerland.
Today Dr. Andre Waismann is the head of the ANR Unit in Barzilai Hospital in Ashkelon, Israel.
55
Here for more on the work in the Intensive Care Unit at Spital Interlaken
9.3 Feedback from patients
R.S.; 1965
After a case of shingles (Herpes zoster), I contracted post-herpetic neuralgia. Due to this illness, I
suffered from chronic pain in the shoulder and chest area. After trying several methods for pain
relief without success, it was decided I should be treated with opioid-based painkillers. Due to the
constant increase in dosage, I ended up dependent on these medications, accompanied by changes
to my personality. Ultimately, I had to take very high doses every day so that I could still manage
my work. The pain continued to increase, despite steadily increasing the dosage, and I was advised
by my doctor to seek a withdrawal treatment. At the same time, I heard about the ANR withdrawal
method which was not available in Switzerland. So, we traveled to Israel. After the treatment I
became aware little by little that I had been given an entirely new lease on life. I can think clearly
again and participate actively in longer discussions. Before the treatment, I would have had to
summon all my strength for such things. When my family met me at the airport, they were surprised at the visible change that had occurred. The pain of the post-herpetic neuropathy has still
not been completely overcome, but I have received valuable information on how to deal with it.
Successfully applying this information, I saw how the pain disappeared again within a short period
of time without any need for me to take pain medication. As a consolidating treatment, I have to
take medication until further notice to suppress the urge for the opiates.
In summary, I can say that the treatment was a complete success. I am completely convinced of
this method and I hope very much that it will also be possible in the near future in Switzerland,
where medicine is very advanced, to use this method to free people from their dependency on
addictive drugs.
Comment:
This involves one of the first patients treated as part of the ANR Switzerland pilot
project. Nothing has changed in his assessment.
Mr. B.B.; 1952
It has been almost a year since you helped me with opioid withdrawal. First, I would like to thank
you and the entire team for your fabulous work. After it initially went very well, I suddenly had
pain in the area of my stomach and intestines. I could feel stings like needles in my lower abdomen
and my stomach swelled up like a balloon. All evaluations were unremarkable. After five weeks it
gradually got better. Currently I am work part-time and would like to go back to full-time in the
next few weeks. Although there were a few weeks where I regretted my decision, today I have to
say that I am very glad that I participated. I am doing well now, and I am free of opioids. You have
always supported me, and I thank you very much for everything you have done for me.
Comment:
K.Th.; 1960
This patient was dependent on opioid painkillers due to back problems. Luckily, the
back pain improved after the withdrawal. The stomach pain is likely explained by the
gradual release of the year-long opioid blockade in the gastrointestinal tract.
56
Due to complications from back pain, I had to take opioid painkillers for almost seven years. Over
time, the side effects of the opiates made my medical training therapy increasingly complicated,
and the entire motor system responded with strange pain blockades and a sensitivity so pronounced that I could hardly bear to have my clothes touch my body. Ultimately, I had to stop with
the training altogether, and I found myself at a dead end. I could not tolerate a reduction in the
opioids.
I was advised to seek ANR treatment, which I completed in February 2016. Once the "aftermath"
of the treatment had diminished, I realized that the side effects had disappeared, in particular the
unexplainable strong pain that had no direct connection to my original back pain and the muscular
overreaction of the body to the development training. In addition, my body gradually began to feel
normal again.
This resulted in new prospects for my continued recovery process. I am doing better than ever
with the guided developmental training. The advice from the treatment team was a great help to
me. The information on how I could intentionally activate endorphins for pain relief was very
helpful.
I am moving toward the goal of being healthy again with new optimism. I would like to thank the
entire treatment team for their knowledgeable, empathetic guidance on all aspects of the ANR
treatment!
Comment:
This patient showed a noteworthy phenomenon that we have detected again and again
in pain patients – opioid-induced hyperalgesia, meaning that opioids in higher doses
have less and less effect which can cause serious pain hypersensitivity in certain circumstances. This phenomenon is underestimated in the established pain medicine.
57
S.M.; 1971
After six weeks with sustained vomiting and the corresponding repeated hospital admissions, I
underwent in-patient rehabilitation. I had lost 10 kg and the Bechterew's disease hit me full force.
I could only lay in bed and scream with pain. Cortisone didn't help, nor did modern anti-arthritics,
so the doctor treating me prescribed a low dose of opioid therapy with planned substance shift
and pauses. Since the ANR treatment, I have a different attitude toward the opioids – I take them
only when the pain is unbearable, where before the opioids were an addictive substance. I am
proud and happy that I now have the whole thing under control. It has made it possible to have a
life with social contacts again. But with my disease I will always need to take opioids from time to
time. Surely, I will not go back to where I was.
Comment:
This describes the difficult initial situation of a severe pain disorder combined with a
psychiatric disorder and an addiction. The patient took high doses of opioids never before seen by those of us on the team. In formal terms this involves a termination of
treatment with a relapse. On the other hand, the ANR treatment had an overall positive
effect.
U.C.; 1960
I was prescribed morphine for pain for years and decided to undergo the ANR withdrawal because
I had noticed over time that the morphine had changed me a great deal and I had become dependent on it. Since then I am completely free from morphine and am very happy about it. I have only
good things to say about this treatment and I would always recommend it. I was given very professional advice by the team before I made my decision.
Since the treatment I have had absolutely no urge for morphine, and I have found other ways to
deal with the pain and help myself as needed with light painkillers, physical therapy, and sports
(to the extent that is possible for me). I was very well cared for throughout the treatment, and in
the days, weeks, and months afterward I could contact the team any time I needed to.
The only negative point is that the costs were not covered by the health insurance fund. In my
opinion, the method is much more cost-effective than other therapies offered that are associated
with weeks of hospital admission and require even longer psychological treatments. In my opinion the method is very efficient and effective.
Comment:
The initial situation was not quite clear, particularly since this patient also indicated
a phase with illegal heroin use in addition to the pain disorder. The result was, as with
all treated patients, the complete disappearance of the (physical) urge for opioids.
A.R., 1977
I am the sister of A.R. who received treatment from you. I thank you, as well as those involved,
very much for that! I can hardly comprehend what happened...after 20 years filled with hope,
doubt, and fear! Filled with joy, I wish A.R. a happy, meaningful life. He has a lot of catching up to
do! Once again, thank you very much!
Comment:
This patient had terminated treatment after about four months due to a lack of daily
structure and failure to change environment.
E.S.; 1976
I am still working through the process. I had a tough time right after the hospital stay. A trip to
Hawaii made a clean break possible. Currently I am in the process of integrating into the job market. Due to marijuana use, I had to move out of my parents' home. I no longer use heroin, and I
take the Naltrexin regularly.
Comment:
This patient showed convincingly that the psychosocial deficits often do not emerge
until after the ANR treatment. This requires greater attention and awareness in the
follow-up phase.
58
Mr. B.B.; 1952
It has been almost a year since you helped me with opioid withdrawal. First, I would like to thank
you and the entire team for your fabulous work. After it initially went very well, I suddenly had
pain in the area of my stomach and intestines. I could feel stings like needles in my lower abdomen
and my stomach swelled up like a balloon. All evaluations were unremarkable. After five weeks it
gradually got better. Currently I am work part-time and would like to go back to full-time in the
next few weeks. Although there were a few weeks where I regretted my decision, today I have to
say that I am very glad that I participated. I am doing well now, and I am free of opioids. You have
always supported me, and I thank you very much for everything you have done for me.
Comment:
This patient was dependent on opioid painkillers due to back problems. Luckily, the
back pain improved after the withdrawal. The stomach pain is likely explained by the
gradual release of the year-long opioid blockade in the gastrointestinal tract.
E.C.; 1976
ANR was the best thing that could have happened to me. When you have the will and the necessary
motivation, you can successfully leave a life of drugs with ANR. My motivation was my son, my
mother, and the desire to have another child.
My problem was my fear of the withdrawal, because I had experienced terrible vomiting with previous withdrawals. After the ANR treatment I still did not feel especially well, but I had no "withdrawal" and especially no vomiting, which for me was half the battle.
However, I could hardly sleep, and my body temperature fluctuated between hot and cold. Both
disappeared with time, and in fact without new medications. Except for the Naltrexin, of course,
which I still have to take for a few months.
I thank Dr. Waismann once again for his procedure which has made it possible for me to have a
new life, and I wish him only the best.
Comment:
This patient was in a heroin program for several years, was a mother, and had a permanent job as well as no connection to the drug scene. Due to earlier experiences, she
never wanted to undergo conventional withdrawal again. In this sense, ANR was her
only chance for drug-free life.
N.M.; 1977
The patient is doing very well after a very difficult initial phase. He became a father a few weeks
ago.
Comment:
F.M.; 1972
We are confronted again and again with a "difficult initial phase". It plays a key role
in the early follow-up care phase.
59
I wish you and your entire family a wonderful Christmas. Thank you once again for giving me a
new life. I am thinking of you.
Thank you for your work. I currently have close and good contact with my brother M. It's a shame
that our mother did not live to see this...I think the contribution of ANR is a complete success. In
any case, for my part once again thank you very much and continued success. (Statement from the
brother.)
Comment:
Before treatment this patient weighed only 47 kg. After discharge he told me he
would have committed suicide if the procedure had not worked. He is working full
time again.
S.P.; 1979
It is moving forward, step by step. I have started working out in the fitness center 3-4 times a
week. My body is responding positively to that. Metabolism, etc. is adjusting and I am already noticing when I only drink one beer, I feel listless, just not good. I force myself to drink a lot of water.
I am traveling to France soon and I will try to stop smoking while I am there. This is a decent
hurdle, but I will be able to do it. As you see, I am still hanging on and moving forward. I would
like to thank you once again for the huge opportunity and the new life to which you and your team
have made such a big contribution. I am very, very lucky.
Comment:
This patient from the first round of treatment in Switzerland has completed an impressive change both outwardly as well as in his personal attitude, and since then has motivated some addicts from his circle of acquaintances to undergo treatment.
S.M.; 1971
After six weeks with sustained vomiting and the corresponding repeated hospital admissions, I
underwent in-patient rehabilitation. I had lost 10 kg and the Bechterew's disease hit me full force.
I could only lay in bed and scream with pain. Cortisone didn't help, nor did modern anti-arthritics,
so the doctor treating me prescribed a low dose of opioid therapy with planned substance shift
and pauses. Since the ANR treatment, I have a different attitude toward the opioids – I take them
only when the pain is unbearable, where before the opioids were an addictive substance. I am
proud and happy that I now have the whole thing under control. It has made it possible to have a
life with social contacts again. But with my disease I will always need to take opioids from time to
time. Surely, I will not go back to where I was.
Comment:
H.M. ; 1987
This describes the difficult initial situation of a severe pain disorder combined with a
psychiatric disorder and an addiction. The patient took high doses of opioids never before seen by those of us on the team. In formal terms this involves a termination of
treatment with a relapse. On the other hand, the ANR treatment had an overall positive
effect.
60
Hello, Doctor! I'm doing very well, thank you. The first few months after ANR were not always
easy. But now, I've found all my energy again and my life is much better! I sincerely thank you
once again for your and Dr. Waismann's work. Sincerely.
Comment:
This patient was in a heroin program for several years before ANR because all other
treatments had failed. Today he is studying languages at a university in western Switzerland.
I.R.; 1963
In the end of August 2013, I was able to go through the ANR withdrawal in Interlaken. Since that
time, I have abstained from all conscious-altering substances. I have rebuilt my life and my social
structures and am once again a productive member of our society. I look forward to working at an
80% full-time position as a caregiver for the disabled. It doesn't work "just like that". It takes my
desire and will to live drug-free. The ANR treatment has helped me an amazing amount. Many
thanks to all those involved!
Comment:
This patient had previously been in withdrawal clinics countless times, usually for
several months, because depressive episodes and suicidal crises always played a role.
I.M.; 1978
You were certainly one of the most important people in the life of Mr. I. After the ANR treatment
he had difficulty with the real world, with our system, and with himself. He was suddenly able to
think clearly and coherently without escaping again in the drugs. The memory of many terrible
things during his dependency (etc.). He was very ashamed and had severe depression, hardly
wanted to keep living. Today, just seven months after the treatment the current development is
very encouraging. The family is delighted. There was only one relapse with cocaine. Currently he
is working eight hours a day, helps other people, and is slowly getting a better grip on everyday
life. We thank you for this type of treatment. You would recognize the difference in him immediately. (Patient's coach)
Comment:
After exactly one year, the patient decided to return to a life of drugs. This seems to
better suit his revolutionary essence...
T.St.; 1970
I would like to thank you from the bottom of my heart for you work. The word is a limitation,
because there is much more that I would like to get across to you. I no longer need additional
medications and I feel so awesome that I can hardly put it in words. I feel free and feel new energy
for my projects.
Comment:
St.P.; 1972
Before treatment this patient needed only small quantities of methadone, but always
failed at the last 5-10 mg.
61
It is going very well for me, I can live again and enjoy my family. My heart is filled with great joy!
The people around me can't believe their eyes, they see a new person. My sleep has changed, I
don't have to sleep as much and am usually well-rested early in the morning.
Comment:
This patient has an impressive story. Most psychiatrists would have certified him as
having a difficult and chronic addictive personality, especially with his history of severe
[physical] abuse.
St. D.; 1970
Normalcy is slowly returning. I still feel very weak but have been able to go paragliding again.
Head and body are coming together gradually. Today I am starting an exercise program (running,
strength training) to improve a bit. Sleeping is going reasonably (up to four hours). Currently only
the weakness in the evening and the headaches are still causing problems. I am optimistic that
this will improve again. Thoughts of drugs have no response whatsoever. I cannot imagine every
using anything.
Comment:
This patient was stable for several months after ANR but suffered a difficult stroke of
fate that he dealt with by returning to drug use. As a result, there were severe medical
complications.
Z.F.; 1974
62
I am doing very well, except for a bout with the flu which in itself was a stimulating experience. I
am in great shape now and for the past two weeks 100% involved in the work process. All of that
does not use my full capacity, though, so I am adding other things like sports, additional hobbies,
errands, etc...I am also noticing that I am drawn to people – I used to be quite the recluse, now I
am much more alert and social.
The only thing that is still not worked out, and will probably still take time, is my sleep. I still
wake up half the time, usually sweaty, and I still don't seem to dream, at least not that I recall.
But after a long dry spell for my body that is all that is left to work out.
I am extremely grateful that I have been given this opportunity to participate in the ANR procedure which impressed me from the very start. I have gotten back my life, my family, my body,
and so much more!
Comment:
This patient was in a heroin program for several years, had a family and a job, and no
more connection to the drug scene. Unfortunately, he took cocaine one time at a party
and could not sleep for several nights. His "old" cure was a small dose of heroin. This
resulted in a relapse. He was treated a second time, this time with success.
O.T.; 1971
My Santa Claus did come already a long ago. He came when I was in Interlaken. I was given a new
life and I feel absolutely great. I never thought the result of my stay in Interlaken would be so
astonishing. My urge for dope is completely gone. Even when I was visiting my dealer and he was
waving a bag of brown powder under my nose and I could smell the taste of it – nothing happened.
Before I would have got a sweaty nose and moist hands. Absolutely nothing - unbelievable...! Before I always knew, even when I stopped taking dope, that the desire to take “H” would accompany
me till death. Now for the first time in my life, I really feel, that my problem is gone forever and
will never occur again. For this I thank you until the end of my life. You are great guys...
Comment:
Interesting case because the patient showed a severe dependency despite only sporadic
use, which he became very aware of only after the treatment.
W.C.; 1956
The treatment itself was more intense than expected due to my very heavy cocaine use. The first
night I had to fight through strong pain and restlessness. The pain disappeared on the following
day, as did the restlessness. I still felt very weak but very good and satisfied. The weakness lasted
for a few days, as did the diarrhea. I found the treatment at Spital Interlaken to be very pleasant.
The meetings with the team were very helpful. My husband and I felt well informed and supported.
I had serious misgivings that the mental problems would flare up because I suffer or had suffered
from post-traumatic stress disorder. However, I quickly felt very even-tempered and had no crisis
related to this. The stress disorder is still there but I was able to take big steps forward because I
have a clear head now and can process this differently. I never had withdrawal symptoms or cravings. However, I can't say how it will go without Naltrexin.
In summary, I would like to say that this was probably my last chance, I used it, and it has worked.
Thank God.
Comment:
Due to the PTSD, the prognosis was unclear. But with this patient a phenomenon manifested that we have observed again and again – mental disorders experience a significant improvement or even disappear entirely after the treatment.
63
9.4 Helpful Metaphors to Explain ANR
Of goldfish and sharks
The human body has a system that takes on a central role in nerve metabolism, similar to the wellresearched serotonin and dopamine metabolism: the endogenous opioid system. The substrate
for this system are the endorphins described in section "xyz". These likewise well-researched endogenous opioids act as biochemical neurotransmitters which could trigger nerve signals on the
corresponding receptors with psychological effects, but also purely somatic processes (e.g., in the
gastrointestinal tract).
When you observe the possible stimuli for endorphins, the following image illustrates the comparison of a normally functioning endogenous opioid system with system overstimulated by externally supplied opioids: a goldfish pond, its biological balance with comparably "small bits of
food" – meaning the endorphins in micrograms – is ensured. The goldfish represent the opioid
receptors. Normal everyday activities are sufficient to stimulate the "happiness hormone" and so
create a balance with bio-psycho-social well-being in the goldfish pond.
If opioids are taken from external sources on a regular basis in higher doses (milligram to gram
range) and for longer periods of time, this system changes drastically. As described in section
"xyz", the number, density, and probably also the affinity ("hungriness") of the opioid receptors
increases. In the figurative sense, there is no longer a modest goldfish pond, but rather a tank of
hungry sharks! Their hunger grows with the duration of the dependency. A certain amount of food
(= opioids) must be ingested regularly so that the system can be in balance. Otherwise the sharks
become restless which in the figurative sense corresponds with the withdrawal syndrome.
Interestingly, opioid addicts can identify
very well with this image at the first meeting.
Most of them have already been suffering for
years or even decades with "sharks in the
head" – the craving for opioids when the supply is lacking.
The ANR treatment therefore includes the blockade of excess opioid receptors (sharks) while protecting the original endogenous opioid system (goldfish). This means that under the initial ANR
treatment, the sharks are basically stunned and perish during the minimum of one year that the
blockade is kept in place. After no longer than one and a half years, there are no more sharks in
the pond, the blockade can be lifted, and the treatment is complete. In this context, it should be
noted that these processes, i.e., the (down) regulation of opioid receptors, also adjust after a conventional withdrawal, but much more slowly. Instead of one and a half years, this process could
take five to ten years. This could be one explanation why after several years of living drug-free
some addicts can develop a barely controllable craving under certain circumstances (e.g., smell),
and in some cases a relapse is provoked.
64
A brief anecdote
Today, the almost 50-year old patient H. had his experiences with drugs at the Platzpitz and Letten
train station, the notorious open drug scene in Zurich in the 1980's and 1990's. After several unsuccessful withdrawal treatments, he was finally able to leave, and he completed about two years
of inpatient addiction treatment in Basel. After about five years of living drug-free, he was offered
heroin at a party, and it was literally placed right under his nose. This triggered a cascade in his
brain which almost "automatically" led to a relapse with several months of withdrawal again. Still
today he cannot understand what happened in his brain back then.
After failed attempts at withdrawal he underwent medication assisted treatment in a newly-created heroin program. He was made aware of Dr. Waismann in Israel by one of his mother's acquaintances - her son had been successfully treated there. So, H. was also treated in Israel. About
three months after the treatment he wanted to unenroll from the heroin dispensary – but he
turned around at the door because he was afraid of having the same reaction that had caused him
to relapse years earlier. Dr. Waismann advised him by telephone that he should confidently enter
the dispensary, and that neither the smell nor the special circumstances there would have an effect. And that was indeed the case...
Today H. has been the managing director of a small informatics company for more than ten years,
is married, and a father of three children.
65
A brood of vipers
A man in eastern Switzerland has made a career of his hobby. In his large basement he keeps
dozens of the most poisonous snakes, including cobras, mambas, and rattlesnakes. He has informed the police and the fire department how to properly capture a snake with a hook and a bag
without risking a life-threatening bite.
After a television show about this man, my subliminal fear of snakes gave me a terrible nightmare.
I was standing in the middle of this basement and the poisonous snakes were out of their cages,
slithering around my feet. Finally, the snake trainer came and hauled one poisonous snake after
another back to their cages.
These processes are an illustration for the
processes involved in the ANR procedure.
The snakes stand for the craving, or the urge
for opioids. This determines practically
every step by the opioid addict, causes a
lack of freedom, and is ultimately a potentially lethal impulse.
Catching the snakes is like the blocking and sealing of the opioid receptors, and the Naltrexon is
like the latching mechanism on the terrariums. This latch must be replaced every 24 hours; otherwise the cages will open again due to the half-life (decay time) of the Naltrexon on the receptor.
This means that the Naltrexin disintegrates if it is not renewed after 24 hours, i.e., the snake cage
opens, and a snake will escape in the hours that follow.
If the snake is outside of the cage again, there is no longer any benefit in closing the cage, or starting the Naltrexin again. The escaping of the snakes means craving and this in turn in about half of
the cases of opioid use!
This horror story is a helpful image for illustrating the need for consolidating and uninterrupted
Naltrexin intake after the ANR treatment.
66
9.5 The ANR Treatment Team
Dr. med. Patricia Manndorff
Anesthesiological Screening, Treatment in Hospital
Specialist in Anesthesiology and Intensive Care Medicine FMH
Head Physician at the Klinik für Anästhesiologie und
Intensivmedizin Spitäler FMI Interlaken [Clinic for Anesthesiology and Intensive Care Medicine]
Member of Executive Board
Medical studies at the University of Freiburg in Breisgau
Clinic for Vascular Surgery, Anesthesia, and Intensive
Care Medicine in Villingen-Schwenningen (Germany)
Clinic for Anesthesiology Thun Hospital
Clinic for Anesthesiology and Intensive Care Medicine
Spitäler FMI Interlaken from 2002
Lives in Interlaken, Canton of Bern
Married, three children
Specialist in Psychiatry and Psychotherapy FMH
Head Physician for Psychiatric Services for
Spitäler FMI AG [hospital management company]
Studies in human medicine at the Universities of
Basel/Geneva and the University of Wisconsin
(USA). Training as a specialist in psychiatry and
neurology at the University of Wisconsin
Teaching assignments at the Universities of Fribourg and Bern
President of the foundation Pro Mente Sana
Lives in Interlaken and southwest England
Dr. med Thomas Ihde-Scholl
Psychiatric Screening, Consultations
Dr. med. Daniel Beutler-Hohenberger
Information, Pre-evaluations, and Follow-Up
Specialist in General Internal Medicine FMH
Focus on dependency disorders
Primary Care Physician in Thun
Initiator of the ANR Switzerland Pilot Project
Studies in human medicine in Bern
Further studies in Internal Medicine, Surgery, and
Psychiatry
Responsible Physician for Drug Withdrawal Clinic
"Marchste" in Kehrsatz
Publishing activities
Lives in Gwatt near Thun
Married, five children
67
68