This review (2014) evaluates the use of LSD, peyote, ibogaine, and ayahuasca in the treatment of dependencies and the possible mechanisms underlying these treatments, including the notable “after-glow” effect that in part reflects their action on the serotonin neurotransmitter system.
Abstract
“Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950’s and 1960’s they were largely prohibited in medical treatment and human research starting in the 1970’s as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable “after-glow” effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics’ well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.”
Author: Michael Winkelman
Summary
Introduction
Psychedelics, hallucinogens, entheogens, psychointegrators and sacred medicines have been used in ethnopharmacologies for thousands of years, but have been largely excluded from human research and treatment since their broad international prohibition in the 1970’s.
While it might seem incongruous to treat addicts with substances that are generally classified as Schedule I substances, there is evidence that suggests that psychedelics are both reasonable and effective treatment for many conditions.
Psychedelics have been recognized as having significant effects on the serotonin neurotransmitter system, which is another significant reason for their use in addictions treatment.
Lysergic Acid Diethylamide (LSD) in the Treatment of Alcoholism
LSD is considered to be a synthetic chemical, but it has natural analogues in the ergot alkaloids found in a number of plants. LSD has been used to treat alcoholism since the 1950s, and it has been credited with providing motivation for recovery.
Early studies of ketamine were limited in their methodological designs and follow-up periods, but Halpern has shown that there are some valuable findings and applications to be culled from this early research.
Meta-analyses of early studies using LSD for addictions treatment show that LSD was effective in treating alcoholism, with improvements greater than 50% over control groups.
Six randomized controlled trials were conducted on patients being treated for alcoholism. The results showed that LSD provided a significant beneficial effect in the treatment of alcoholism in the short-term (3 month) and medium-term (6 month), as well as differences at long-term follow-up which were not statistically significant.
Krebs and Johansen concluded that a single dose of LSD can produce significant reductions in alcohol abuse, but that these effects have declined by the 12 month follow-up.
A psychedelic model of treatment for alcoholism is more effective than a psycholytic model, because large doses of psychedelic drugs that produce life-transforming cosmic experiences are necessary to change one’s self-concept and lifestyle.
Serotonergic Effects
The therapeutic mechanisms underlying the psychedelic treatment of addiction in general come from effects on the serotonergic neurotransmitter systems. Serotonin enhancement effects cascade into other neurotransmitter systems affected by addictions.
Bogenschutz and Pommy [18] propose that the therapeutic use of psychedelics can affect the mechanisms that mediate recovery from addiction through the activation of the serotonergic system, which reduces craving, anxiety, and improves mood.
Psychedelics can contribute to drug use cessation through the induction of mystical experiences, personality changes, a heightened awareness of negative consequences of drug use, a sense of self-liberation and relief, and a reevaluation of one’s environment.
Alteration of Consciousness
The therapeutic effects of psychedelics in the treatment of addictions involve the alteration of consciousness and the myriad of healing effects produced. These effects include a sense of connection with nature and others.
A wide variety of means of altering consciousness, including drug and non-drug procedures, have basic similarities. These include high voltage slow wave EEG activity, parasympathetic dominance, interhemispheric synchronization, and limbic-frontal integration.
Psychointegration
Winkelman characterizes the effects of psychedelics as psychointegration, and explains that this term reflects the similar effects of these diverse substances on the serotonin system, which is a neuromodulator that regulates the balance among many neurotransmitter systems.
Psychointegrators induce synchronized alpha and theta brain wave hyperactivity across the neuraxis, the nerve bundle linking the structural levels of the brain from the brain stem to the frontal cortex. These processes produce a relaxation response and physiological integration of behavioral, emotional, and cognitive processes.
Psychointegration occurs when psychedelics affect neural, sensory, emotional, and cognitive processes, enhancing consciousness through integration of normally unconscious emotional and self information into the frontal cortex and consciousness.
Peyote and the Native American Church as Addictions Treatment
Peyote is a sacrament within the Native American Church that contains mescaline, a stimulant similar to ephedrine and amphetamines. Its physiological effects involve alterations of consciousness that can be induced through nondrug means.
The Peyote Religion rejects the use of alcohol, making the NAC a natural support group for recovering alcoholics. The NAC uses peyote in an all-night meeting during which all the community may participate in the singing, prayers, chanting, and drumming.
The overnight nature of the activity contributes to the typical visionary experiences predicting one’s future ruin as an addict. The NAC also addresses addiction through social psychological mechanisms, forming a sense of community that promotes a new identity and a social support group that does not use nor tolerate alcohol use.
Peyote is a cultural psychiatry that manipulates consciousness in order to promote socially-valued patterns of ritual experience, self awareness and emotional control. It has many effects on social, psychological and emotional well-being, and may be particularly relevant for Native American groups deprived of their own spiritual traditions.
Mechanisms of Therapeutic Effects
The physiological effects of peyote, apart from the ritual context provided by the Native American Church, should not be completely discounted. These effects include enhanced affect and an increased openness to communication regarding one’s problems, making them more accessible to therapeutic intervention.
Ibogaine Use in Withdrawal Cessation
Ibogaine, an extract from the root of the iboga plant, was used in rituals, to enhance hunting skills, and for divinatory purposes, and was also used by the Bwiti secret societies of Gabon and Congo to re-establish social stability and well-being.
Ibogaine was discovered in the early 1960s to be effective in the treatment of drug addiction in informal experiments carried out by Howard Lotsof in New York City. It has remained available in alternative non-medical treatment settings around the world.
Ibogaine is used for addictions treatment around the world, and has been shown to reduce withdrawal cravings and addictions. It also has a short term effect in reducing cocaine addictions that lasts several weeks to months.
Ibogaine is used in addict communities and medical subcultures without the ritual and ceremonial aspects associated with the indigenous traditions, but there are also other models, including spiritual ones. The drug induces high density images of autobiographical nature and central to life narrative, and provides psychological insight into the drug use.
Brown reviews the substantial evidence regarding the effectiveness of ibogaine, pointing out that it has been shown to reduce or even eliminate withdrawal symptoms from a variety of drugs, especially opiates and cocaine.
Mechanisms of Therapeutic Effects
Ibogaine’s therapeutic effects are likely similar to those of other psychedelics that have effects of serotonin transmission, including the frequent comments made by the clients that they were given insights into their past and forced to accept the impact that their addictive behaviors had on their families and friends.
Alper & Lotsof propose that the primary mechanisms of action of ibogaine are not derived from effects on opiate or serotonin receptors, but rather from effects on the inferior olive of the brain stem and the Purkinje cells, which produce prolonged tremors and eliminate previous behavioral patterns.
Ayahuasca in Addictions Treatment
Ayahuasca is a combination of two plants, Banisteriopsis caapi and Psychotria viridis, which contain several monoamine oxidase (MAO) inhibitors. The Psychotria contains the active ingredient, DMT, but the Banisteriopsis is considered the more important plant.
Ayahuasca has been used for a wide range of purposes in pre-modern, modern and post-modern contexts, including shamanic development, community-wide rituals, and contacting spirits of the dead.
There are many treatment centers using ayahuasca, but there are no formal clinical evaluations of outcomes using double-blind clinical studies. However, there is a range of evidence that ayahuasca rituals can positively affect addiction outcomes, especially for those who have a long history of relapse and treatment failure.
The Takiwasi Program
The Takiwasi program takes the ritual approach to treatment seriously, incorporating traditional medicine approaches at organic, psychological and spiritual levels. This allows for deep personal reorganization.
The Takiwasi treatment program begins with a physical detoxification, addresses the consequences of withdrawal and dependency, and provides access to deep levels of the personal unconsciousness, particularly repressed memories. The patient becomes their own healer, taking personal responsibility for the healing processes.
The Takiwasi program begins with ten days of isolation, followed by two months of detoxification, meditation, music therapy, saunas and relaxing teas. After this, family visits are allowed, and ayahuasca and other ASC induction techniques are used to reveal unconscious material for therapeutic work.
Ayahuasca ritual treatments produce positive effects because of the physiological properties of the ayahuasca, its interaction with the patients’ psychological condition, the environment, and the social relations with therapists and other participants in the treatment center.
Institute of Applied Amazonian Ethnopsychology
The Institute of Applied Amazonian Ethnopsychology (IDEAA) uses ayahuasca in a minimalist approach that includes psychotherapy, breathing techniques, psychodrama, and bibliotherapy, as well as massage, colonic irrigation, shiatsu, and naturopathy.
Ayahuasca-ritual practices involve reviewing one’s past, having powerful emotional experiences, dying, experiencing nature, and having transpersonal or transcendental experiences.
Religious Participation as Ayahuasca Therapy for Addictions
People with a history of alcoholism who joined the Brazilian ayahuasca church Unio do Vegetal underwent profound life changes, including a generous attitude towards others and a restoration of stability to personal and familial relationships.
Psychophysiological Effects of Ayahuasca: Purging, Visions and Psychodynamic Processes
Ayahuasca causes physical effects such as purging and vomiting, as well as visions and the recall of significant past memories. How these effects are interpreted within the ritual and personal circumstances are important to the recovery processes.
Ayahuasca visions can help people to recover repressed memories of traumatic events and provide insights into patterns of psychological functioning that support addictive lifestyles. These insights can help them to make the changes necessary to resolve interpersonal problems.
Ayahuasca’s psycholytic effects can aid in addictions treatment by facilitating the release of repressed emotions and providing awareness of the likely future consequences of addictive behaviors.
Ayahuasca stimulates psychological process by forcing a confronting of oneself, revealing patterns of behavior, and producing transcendent and mystical experiences. These experiences eliminate the craving for drugs.
Ayahuasca’s effects may be mediated through increased activity in the right hemisphere’s anterior insula, anterior cingulate/frontomedial cortex, and left hemisphere’s amygdala/parahippocampal gyrus structures, which enable repressed memories to be made consciousness and re-experienced emotions associated with them.
Loizaga-Velder and Loizaga Pazzi [61] found that ayahuasca induces body-oriented effects that provide relief of stress and an experience of detoxification associated with the emetic effects that produce an attenuation of craving.
Ayahuasca experiences can lead to a sense of self-destruction, which helps addicts make changes in their behavior. The prolonged social contact among participants helps to develop a sense of belonging that motivates lasting behavioral changes.
Mate [62] proposes that ayahuasca is capable of successfully treating a wide range of conditions, including addiction dynamics, by helping to bring unconscious psychological conditions and stress into consciousness and liberating the person from these influences.
Formal Assessments of Ayahuasca Treatment Outcomes
Fernández et al. [63] used formal assessments to show that the combination of ayahuasca and ritual produced significant improvements in personality, psychopathology, and neuropsychological conditions in hopeless and problematic drug users who had failed in other treatments programs.
A preliminary observational study in a First Nations community in Canada found that ayahuasca use improved mindfulness, hopefulness and empowerment, as well as quality of life meaning and outlook, but did not reduce cannabis or opiate use.
Biochemical and Physiological Mechanisms as a Basis for Ayahuasca’s Effects on Addiction
Prickett and Liester propose a variety of biochemical and physiological mechanisms by which ayahuasca might effectively treat addictions. These mechanisms include direct and indirect actions on both dopaminergic and serotonergic systems.
Ayahuasca can increase and decrease dopamine levels in the mesolimbic dopamine pathways, thereby reducing craving and withdrawal symptoms. This is achieved through multiple mechanisms that provide opposing mechanisms that both raise and lower dopamine levels in the mesolimbic dopamine pathways.
Prickett and Liester [65] review primary research establishing mechanisms of action of ayahuasca constituents, specifically the beta-carboline alkaloid harmine from Banisteriopsis and the DMT normally sourced from Psychotria viridis. These mechanisms may be involved in the potential anti-addictive therapeutic effect of ayahuasca.
DMT’s affinity for 5-HT receptors provides a mechanism for dopamine elevation in the MDP, while binding to serotonin receptors provides a mechanism for lowering dopamine in the MDP by inhibiting dopamine release. Ayahuasca balances dopamine levels in the MDP between low levels that produce withdrawal symptoms and elevated levels that lead to addictive behaviors.
Prickett and Liester propose that the therapeutic effects of ayahuasca may be due to its ability to alter the synaptic connections of neurons. This process is thought to underlie the addiction learning process.
Ayahuasca can affect neuroplasticity by effects on neurochemicals and pathways, facilitating adaptive changes in neural architecture, and facilitating the disruption of pathological associations that underlie addictive behaviors.
Ayahuasca affects the brain’s BDNF and gabaminergic and glutamaturgic systems, which are involved in producing neuroplastic processes that alter old circuits that supported maladaptive addictive behaviors and allow for the production of new more adaptive behaviors.
Assessment Of The Effects Of Psychedelics In Addictions Treatment
Phase I studies are intended to evaluate safety, side effects, and safe dosage range of novel substances. These studies may also rely on patient populations that have the possibility of showing risks where none would exist in normal populations.
Phase II trials use small groups of strictly selected patients to further evaluate safety and to determine effectiveness and ideal doses for targeted illnesses. They do not always include double-blind studies, but may still include placebo effects.
Phase III trials use randomized clinical trials with large groups of patients, and double blind controls to assess the role of placebo or expectancy effects.
Treatment of patient populations begins with Phase II studies, once issues of toxicity and safety have been determined. While Phase II to Phase IV studies are still assessments, they are based on the active use of treatments, albeit not approved for the general patient population.
If we assess the effectiveness of LSD as a treatment for alcoholism, we can conclude that it is effective in terms of Phase I and II studies, and that there is a need for further studies to refine knowledge regarding ideal dosage levels, any potential side effects, and the long term benefits.
Peyote
While there are limited toxicology studies, evidence exists regarding the relative safety and effectiveness of peyote as a treatment. In addition, the Indian Health Service approves reimbursement for the use of peyote for the treatment of alcoholism among Native Americans.
Further research might consider using synthetic mescaline instead of peyote, and determining the possible strictly pharmacological effects as opposed to the ritual contributions to addiction cessation.
Ibogaine
Many forms of information, including case reports, preclinical toxicological evaluations, initial Phase I trials of safety pharmacokinetics, and animal studies, support the use of ibogaine to attenuate withdrawal and reduce craving in humans.
There are safety concerns regarding the use of ibogaine in addiction treatment centers, especially the risk of death. However, there is an extensive manual available for screening of patients, including guidelines for pretreatment laboratory tests, monitoring of patients during the treatment process, and appropriate emergency personnel and medical intervention.
Ayahuasca
Evidence of the safety of ayahuasca is derived from several studies, including studies of youth and long term members of the ayahuasca churches. While double-blind clinical trials are challenging, they are not necessary to justify further use of ayahuasca.
The evidence for ayahuasca as an effective treatment for addictions is from practices that emphasize the interaction of sacrament with physiological effects with the ritual and interpersonal dynamics of therapy.
Conclusion: Policy Directions in Therapeutic Development
Psychedelics reduce addictive behaviors through biological mechanisms, but also through psychosocial, spiritual and ritual effects.
The psychedelics have shown exceptional potential as part of substance abuse rehabilitation strategies, and have been validated by many forms of evidence, including animal studies, laboratory data, medical case studies, personal case accounts, and case series.
The U.S. federal prohibition on psychedelics is considered by many to lack constitutional grounds, since there is no article in the constitutions or amendments to the constitution that allow the federal government to regulate what we put into our bodies.
Winkelman and Roberts have provided an overview of the multiple levels of society at which we need to act to change the current political climate that regulates these substances.
Fenney expands our understanding of the possible permissible uses of these substances and contends that the legal system cannot logically-or perhaps even legally-deny the same rights to other ethnic groups in society.
Education, public policy development, and collective political action, rather than just more science, is necessary for changing opportunities for the use of psychointegrators in treatment of some of the most ravaging social diseases of our times.
Physicians have a moral imperative to seek the applications of psychedelics in addiction treatment. Phase III clinical studies are needed to confirm their effectiveness and monitor possible adverse drug effects and drug interactions.
Because of the cost of Phase III studies and the imitations on patenting natural substances, the drug industry is disinterested in further clinical trials, even where there are approved drugs that also have a demonstrated effectiveness in addictions treatment.
Psychotherapists have limited therapeutic options for the use of psychedelics, but the medical necessity defense may be a valid defense if the use of the substance reduces the patient’s severe suffering without causing disproportionate harm to others.
A recent study found that naturalistic hallucinogen use reduced recidivism among individuals with a history of substance use and high rates of recidivism who were under supervision in a community corrections program.
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