A Trip to Sobriety: Psychedelics and Addiction

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The idea of ingesting one drug to combat addiction to another may seem strange to some, to others, heretical. There is, however, a growing body of evidence to suggest that some substances may hold potential for combating addiction, and the most promising of these are the psychedelics.

Addiction is incredibly costly to society as a whole, exerting a vast toll on the lives of many and imposing a huge burden on the global economy. Tobacco and alcohol addiction alone have a huge impact. Smoking is the leading cause of preventable premature death globally due to its causing a wide range of non-transmissible diseases. Smoking will claim the lives of up to two-thirds of all long-term tobacco users, with smokers tending to die 10 years before non-smokers. One recent estimate of the global annual economic cost of smoking estimated it at around $US 1.85 trillion, or around 1.8% of global GDP. Alcohol is a top risk factor for ill-health and premature death and disability, particularly for individuals between 15 and 49 years of age, and it is associated with a broad range of non-transmissible diseases.

The vast personal toll and economic burden inflicted by addiction are only increasing over time, with only a tiny fraction of individuals with substance use and behavioural addictions receiving effective treatment. In more recent years, opiate addiction has become much more prevalent, and was estimated to cost the global economy around $1.5 trillion in 2020. Given the lack of any really effective treatments for addiction to alcohol, tobacco, and other substances, and the hugely corrosive impact it has on humanity globally, it would be unwise not to explore any potential avenues that may lead to the more effective combating of addiction.

A Brief History of Psychedelics and Addiction

Psychedelics first showed promise in treating alcohol in the first wave of clinical research conducted in the 1960’s and 1970’s (although it should be noted that the rigour and quality of the research have improved since this initial wave of clinical work). One of the early proponents of using psychedelics to treat alcoholism was British psychiatrist Dr Humphry Osmond, the man who coined the term “psychedelic” and “turned on” Aldous Huxley. Working with his biochemist colleague Dr Abram Hoffer, they hypothesised that if LSD was administered to alcoholics, it might induce the delirium tremens, the extremely unpleasant effects associated with acute alcohol withdrawal after a prolonged period of drinking, and so scare people straight. On proceeding with their clinical research, they discovered this is not what occurred under LSD…instead, effective treatment of alcoholism seemed to occur through the psychedelic evoking transcendent states of cosmic unity.

Alcoholics Anonymous co-founder Bill Wilson claimed to have freed himself of his addiction to alcohol through a concoction of the Solanaceous plants henbane and Belladonna, through which he experienced a ‘bright white light’ and ‘a feeling of great peace’, which he interpreted as a spiritual awakening, prompting him to never touch alcohol again. Later, on trying LSD, he saw that it too might have potential for shining light on the path of recovery (with the added benefit that it is far safer and less toxic than Solanaceous plants).

Anti-Addictive Mechanisms of Psychedelics

Psychedelics appear to act in a number of ways that may impact addiction, acting multidimensionally through both neurophysiological and psychological mechanisms. They act on the receptors in the brain associated with drug-seeking behaviour, while reducing blood flow to areas of the brain associated with emotional processing and higher function that tend to be overactive in depression. This help may reign in the negative circular thought patterns associated with addiction. The temporary chaotic state induced by psychedelics seems to weaken reinforced brain connections and dynamics, and the experience provides a window of reflection where people can view their life and addiction issues from a wider perspective.

A qualitative study of participants undergoing psilocybin therapy for tobacco addiction revealed that people gained vivid insights into self-identity, and that the grandeur of the psilocybin experiences overshadowed the short-term withdrawal symptoms from smoking cessation (in fact, some of the individuals interviewed expressed that quitting smoking was one of the least interesting features of their experience with psilocybin).

Psychedelics are well-suited to treating addiction.  They have been used and revered for centuries or millennia in some cases, and they are of very low toxicity and safe when administered in a therapeutic context, and they are not addictive themselves. Overuse of them in quick succession results in the development of rapid tolerance, and if overused, they have a tendency to induce bad trips, which act as a buffer discouraging further heavy use. Addiction tends to centre on the denial or burial of past material, whereas psychedelics tend to bring life issues to the surface, where it is hard to hide from them.

Importance of Mystical Experience and Therapeutic Context

Aligning with the earlier research findings obtained by Osmond and Hoffer using LSD to treat alcoholism conducted in the 1960’s, more modern studies exploring the potential of psilocybin to treat tobacco and alcohol addiction have found that the occurrence of mystical or peak experiences under the psychedelic predicted positive treatment outcomes. One study on individuals receiving psilocybin-assisted therapy for alcohol use disorder reported that spirituality, spiritual intentions, mindset, and positive perceptions of the treatment setting emerged as important predictors of mystical experiences under psilocybin.

Aside from the direct effects of the psilocybin, the therapeutic context in which it is administered in an addiction treatment context should also be highlighted, which encompasses therapeutic support during the psychedelic session, in addition to preparation and follow-up integration prior to and following it. In one qualitative study of people being treated with psilocybin for tobacco addiction, preparatory therapeutic counselling, rapport with study monitors, and a sense of forward momentum once engaged with the study treatment were also perceived as vital aspects of treatment supporting abstinence from smoking.

The temporary chaotic, entropic brain state induced by psychedelics such as psilocybin may provide a therapeutic window where people can view the roots of their addiction with greater levity, while also allowing a state of greater mental malleability and the possibility of retraining the negative circular thought patterns associated with addiction. More work is warranted to better elucidate the contributory role of the therapeutic context when it comes to treating addiction with psychedelics.

Psilocybin is among the most well-researched psychedelics when it comes to substance addiction, but such research should still be considered in its preliminary stages. Clinical research is most advanced in exploring the potential of psilocybin to treat alcoholism and smoking among various forms of substance and behavioural addictions.

Psilocybin and Alcoholism

An initial proof-of-concept study examined the potential of psilocybin-assisted therapy to treat alcohol dependency and reported that psilocybin sessions resulted in abstinence that was maintained at 36 weeks post psilocybin. The intensity of effects experienced during the psychedelic session was predictive of reduced alcohol consumption during weeks 5-8 post-session, and no significant adverse events during treatment were reported.

A larger and more rigorous follow-up study was conducted with a sample size of 95 people, using a double-blind, placebo-controlled randomised controlled trial design, where the effects of two psilocybin dosing sessions were compared to placebo. The percentage of heavy drinking days during the 32-week double-blind period was significantly lower for the psilocybin group in comparison to the control group. However, the percentage of individuals who were completely abstinent from alcohol during the 32-week double-blind period did not differ significantly between psilocybin (22.9%) and control (8.9%). No serious events were reported under psilocybin administration.

A further study on a French population exploring the effect of psilocybin therapy on individuals suffering from alcohol use disorder and comorbid depressive symptoms reported that psilocybin-assisted psychotherapy appeared feasible, acceptable, and safe when administered to recently detoxified patients.

Psilocybin and Tobacco Addiction

Amanda Feilding, the late Founder and Director of the Beckley Foundation, had an experience on LSD where her smoking habit was suddenly revealed as being repulsive to her, motivating her to quit on the spot. She felt this would make a worthy area of research, and through the support of the Beckley Foundation, helped ignite the first Phase I study of psilocybin therapy for smoking addiction in collaboration with researchers at Johns Hopkins.

The results of this first trial were impressive, with 12 of the 15 (80%) former smokers abstinent at 26 weeks post psilocybin, with 10 remaining abstinent at 52 weeks (67%), and 9 abstinent at an average of 30 months (60%). Adverse effects associated with psilocybin were considered mild by trial participants (e.g. fleeting feelings of fear or fear of insanity, and transient headaches).

In a follow-up randomised clinical trial, participants received either a single high dose (30 mg/70 kg) of psilocybin in a therapeutic context or 8 to 10 weeks of nicotine patch treatment. The 42 participants who received psilocybin had over 6 times greater odds of prolonged abstinence from smoking at the 6-month follow-up in comparison to the 40 participants who received the nicotine patch. This suggests psilocybin therapy may hold potential as a treatment for tobacco addiction, with further investigation warranted.

Psilocybin-Assisted Treatment of Other Addictions

One preliminary pilot study investigated the effect of psilocybin-assisted psychotherapy for methamphetamine use disorder and reported no serious adverse events resulting from psilocybin, with methamphetamine craving reduced, while quality of life, and levels of depression, anxiety, and stress observed at 28 and 90 days following treatment with psilocybin were improved in comparison to the pre-psilocybin baseline.

Randomised controlled trials are currently underway to investigate the potential of psilocybin-assisted therapy in treating cocaine, opioid, and gambling addiction, with further trials also being conducted to build on the work already done on alcohol and tobacco dependency.

Potential of Ayahuasca in Addiction Treatment

Ayahuasca is attracting increasing interest for its potential to treat addiction. Addiction expert Dr Gabor Maté views ayahuasca as working on addiction in multiple ways; by allowing users to see the baggage associated with their addiction and appreciate that it does not have to be a part of them, and by allowing them a positive experience of love for the self. Neuroimaging research on ayahuasca has found evidence of changes in brain structure in long-term users, associated with positive changes in behaviour and feelings of life satisfaction, so changes in neuroplasticity within the brain may play a role in its anti-addictive effect

Past studies looking at members of the União de Vegetal (UDV) Church revealed that they felt ayahuasca had a profound impact on their lives, with many members reporting they were better able to see destructive behaviour patterns, with a tendency to discontinue alcohol, tobacco, cocaine, and other drug addictions.

One study assessing the capacity of ceremonial ayahuasca sessions to treat substance addiction in an Indigenous Canadian community reported that increased connectedness with self, others, nature, and spirit was a key element associated with reduced substance usage and cravings. This echoes the sentiment expressed by author and journalist Johann Hari’s observation that “The opposite of addiction is not sobriety. The opposite of addiction is connection”.

Research suggests that the communally connected context of traditional or Indigenous ayahuasca sessions may contribute to the success in addiction recovery, with this group context often lacking from Western psychedelic treatment, which is often more individualised. One qualitative assessment of ayahuasca being used to treat addiction in a traditional Peruvian context revealed that the traditional techniques and other medicinal plants used alongside the ayahuasca sessions (such as plant purges and dietary retreats) supplemented the anti-addictive effect of the ayahuasca.

5-MeO-DMT in Addiction Treatment

One study explored the potential of the powerful psychedelic compound 5-MeO-DMT to treat alcohol use disorder in a sample of 12 participants. A single dose of 10mg of the drug was administered intranasally in a psychologically supportive context. A number of treatment-emergent adverse events were noted by participants (including pain in the nasal passages following drug administration, reactivation experiences, nightmares, and nausea). These were considered mild to moderate in severity and were transient in nature.

A marked increase in alcohol-abstinent days and a substantial reduction in heavy drinking days were noted at week 12 follow-up. Six of 12 (50%) participants reported continuous abstinence of alcohol at this time point, three (25%) had a meaningful reduction in alcohol consumption, and three (25%) had no or limited change in their drinking patterns. In the coming years, research exploring the potential of psychedelics such as 5-MeO-DMT is likely to expand, given the shorter-lasting effects they elicit, which are less demanding on a treatment provider’s time than psychedelics such as psilocybin.

A Brief History of Ibogaine

Ibogaine is the primary psychoactive alkaloid found in the inner rootbark of the iboga shrub (Tabernanthe iboga), which has a long history of use for healing and spiritual purposes in central Africa by groups such as the Bwiti. A key part of its use in a traditional context is the death and rebirth experience of an initiatory flood dose, allowing the user to return to a new beginning.

Ibogaine has generated particular interest for its anti-addiction properties. These properties were discovered accidentally by Howard Lotsof in 1962, who was addicted to heroin at the time. He was gifted some ibogaine by a chemist friend, and when consumed, he had an exhausting 32-hour trip. Going to bed, likely swearing off ibogaine, he woke up the next morning, surprised to find he had no desire to use heroin. This was unexpected and made a great impact on Lotsof, and although not a doctor or a scientist, he campaigned hard for research to be conducted on its anti-addiction effect, and he played a key role in generating initial scientific and medical interest and research into the compound.

Methadone is a standard treatment for heroin addiction, but it acts as a substitution and is a highly addictive opiate itself, so one is simply swapping an illegal addiction for a pharmaceutical one. Ibogaine has a much deeper and broader effect on addiction.

The Anti-Addiction Potential of Ibogaine

One important difference between ibogaine (sometimes described as an atypical psychedelic or oneirogen, or dream inducer) is that it has a direct physiological effect on addiction, through its interactions with receptors in the brain. The ibogaine molecule interacts with many different receptors in the brain, but has a low affinity for them. It acts in a multifaceted way, even on a biochemical level, working in part by resetting receptors in the brain to a pre-addiction state. It can alleviate the withdrawal from drugs such as opiates, which is a big help in breaking the addiction cycle. It also induces a waking dream state, a highly personable experience taking place behind closed eyelids, where one will likely encounter repressed memories and examine past and current life issues, but in an emotionally detached manner. This period of reflection aids in a detached, introspective examination of the roots of one’s addiction and the behaviour patterns associated with it.

Ibogaine is converted to noribogaine by the liver and has prolonged effects, often experienced as an afterglow and mood lift post-session, and this compound is thought to play a role in the anti-addictive effects of ibogaine.

Ibogaine therapy has been reported to diminish opioid withdrawal symptoms and drug cravings, with changes noted at one month after administration of a single dose. Building on this research, an observational longitudinal study conducted in New Zealand (where ibogaine is legal) assessed its effectiveness in treating opioid dependence 12 months after a single dose was administered. Rates of addiction, depression, and opioid withdrawal were all significantly reduced at this timepoint. 

While ibogaine certainly has potent potential as an addiction-interrupting agent, is not a panacea for treating addiction. It can, however, provide a window through which people who have the will can enact change. However, the broader context encompassing usage is important with ibogaine, just as it is with other psychedelics. Factors such as post-session support, helpful lifestyle changes, and the person seeking treatment distancing themselves from situations or people that might have associations with past drug use all warrant careful consideration. Ibogaine requires work and will, on behalf of the person using it, to maximise chances of success.

Ibogaine and GDNF

One standout quality of ibogaine when compared to other psychedelics is that it enhances the expression of a brain protein, GDNF (Glial Cell Line-Derived Neurotrophic Factor). This acts as a potent neurotrophic factor that supports the survival, differentiation, and regeneration of neurons, particularly dopaminergic neurons. GDNF has been linked to the anti-addictive properties of ibogaine, and ibogaine can elicit a long-term increase in GDNF levels, with it being found to upregulate its own expression. GDNF aside, ibogaine has been found to increase levels of other neurotrophic factors in the brains of rats, such as BDNF (Brain-Derived Neurotrophic Factor) and NGF (Nerve Growth Factor).

Other research on rats has found that ibogaine can also upregulate genes and proteins involved in the process of remyelination following chronic opioid usage. Myelin is a fatty substance that envelops nerve fibres (axons) in the form of a protective sheath (similar to insulation on a wire), allowing electrical signals to travel more efficiently between neurons, while simultaneously providing metabolic support. Myelin can become depleted as a result of chronic drug usage, such as long-term opioid addiction and abuse of amphetamines.

Aside from its potential in treating addiction, ibogaine may also have an important role to play in aiding in brain recovery following chronic drug usage. Its ability to increase expression of these neurotrophic factors, particularly GDNF (with its beneficial effect on dopaminergic neurons), may be particularly beneficial to those recovering from methamphetamine abuse, which is particularly damaging to the dopaminergic system, and can also deplete myelin.

Potential of Ibogaine Derivatives

While ibogaine may hold the greatest potential for treating addiction of all the psychedelics, one drawback is that it has a higher risk profile than the others. It affects the heart, prolonging the QT interval, or the electrical pulse that spreads over the heart muscle (which may pose a risk to people with pre-existing heart issues). Its usage also comes with heavy side effects, including severe ataxia, nausea, and bradycardia, and its application for addiction treatment requires strict medical supervision.

However, the ibogaine molecule has been tweaked with the aim of rendering it safer and more easily tolerated, one result of these efforts being the compound 18-methoxycoronaridine (18-MC), a synthetic analogue of ibogaine. Although research on this compound is still in its preliminary stages, 18-MC appears safe in humans and is better tolerated by the body, producing neither the body tremors nor the heart rate changes associated with ibogaine, while retaining ibogaine’s anti-addictive effect. However, there may be a trade-off in that 18-MC does not elicit the visionary effects of ibogaine, which are considered of central importance to the Bwiti. The visions may contribute to its anti-addictive effect by allowing the experiencer the opportunity to examine the roots of their addiction.

Conclusion

It is still early days in the application of psychedelics as agents to combat addiction, with research largely still in the preliminary stages. However, given the hugely corrosive impact of substance and behavioural addictions on humanity, and the lack of effective treatments, further research examining the potential of psychedelics is more than justified. Unfortunately, at the present time, draconian laws and numerous regulatory and financial hurdles stand in the way of any researchers hoping to work with these substances. This could be preventing the treatment of a condition that exerts a vast cost on many human lives and on society as a whole.

Psychedelics remain strictly regulated as Schedule 1 substances across much of the world, with such a designation classifying them as having “a high potential for abuse and no accepted medical use”. The scientific research findings highlighting the potential of psychedelics to assist in treating addiction strongly suggest such a classification does not align with the growing evidence base. Moving forward, further research will hopefully shine a light on how psychedelics might be best applied to free people from the heavy chains of addiction.

Sam Gandy | Community Blogger at Chemical Collective

Sam is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Sam via email at samwoolfe@gmail.com