Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use

This review (2017) looks at the (preliminary) evidence that we have of psychedelics in the treatment of addictions (AUD, SUD). Trials with psilocybin, ibogaine, ayahuasca, ketamine (etc) are showing positive results, but randomized controlled trials (RCTs) are badly needed.

Abstract

“Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.“

Authors: Celia J. A. Morgan, Amy McAndrew, Tobias Stevens, David J. Nutt & Will Lawn

Summary

Indigenous cultures have used psychedelic drugs for thousands of years, but there has been limited scientific research into their therapeutic potential. There is now evidence pointing to the use of psychedelic drugs in the treatment of addiction.

The founder of alcoholics anonymous, Bill Wilson, was treated with lysergic acid diethylamide (LSD) to help him stay abstinent from alcohol. It is now believed that these compounds have helpful therapeutic properties and are poised to change the future of addiction treatment.

LSD is a serotonergic hallucinogen that was first synthesized in 1938. Its psychological effects can vary greatly across sets and settings.

In the 1950s and 60s, LSD was used as a treatment for alcohol dependence. In recent years, this interest has been reignited, with the first study on the acute effects of LSD on brain mechanisms in healthy volunteers being published.

Psilocybin is a compound that occurs naturally in over 200 species of mushrooms. Its psychedelic effects last between 26 hours dependent on dose and individual metabolism.

Psilocybin has been investigated as a tool to treat nicotine addiction and alcohol dependence. In one study, twelve of fifteen nicotine dependent smokers were smoking free at six-month follow up, and 10 were still smoking abstinent at 12-month follow up.

Ibogaine is a psychoactive, indole alkaloid found in the rootbark of a Central African plant called Tabernanthe Iboga. It has received interest as a possible anti-craving and anti-withdrawal aid for drug addiction, primarily opiate and cocaine addictions.

There are no double-blind, placebo-controlled clinical trials on the efficacy of ibogaine to treat addiction, but there have been some well-reported fatalities associated with ibogaine use. Properly controlled experimental research is much needed.

Ayahuasca is an Amazonian psychoactive brew made from Banisteriopsis cappi vine and Psychotria viridis bush, and is taken in religious and shamanistic settings as well as in informal treatment centres.

Ayahuasca consumption is associated with reduced alcohol and drug problems.

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, can be used to induce a psychedelic state. It has a short half-life and good safety profile.

Ketamine psychedelic therapy (KPT) has the potential to treat alcohol dependence, with 66% of patients maintaining abstinence a year after KPT compared to 24% of those who engaged in conventional treatment. However, randomised controlled trials are needed to fully understand efficacy.

Ketamine administration has been shown to increase motivation to quit cocaine abuse, decrease craving and reduce cocaine self-administration.

Psychedelic drugs have different mechanistic actions on different receptors, but all have similar long-term effects.

Ketamine has emerged as a rapid acting and potent antidepressant, and psilocybin has shown preliminary evidence of efficacy in treatment-resistant depressed patients.

Depression occurs very frequently in addiction and may be a key factor in precipitating relapse. Psychedelic drugs may also switch off or disrupt the brain circuits involved in ruminative thinking.

Ketamine, an NMDAR antagonist, increases neuroplasticity in the hippocampus by increasing the expression of brain derived neurotrophic factor (BDNF). This increases synaptic plasticity and memory, and is a promising candidate neurobiological mechanism for the lasting changes in behaviour seen following psychedelic and dissociative drugs.

A limited number of studies have investigated the effects of classical hallucinogens on the brain. These studies suggest that LSD, DOI, and ibogaine increase gene transcription and neurotrophic factors in the brain.

Across all compounds, the intensity of the subjective effects correlates with reductions in substance use. The mystical experience is associated with a different perspective on life and a sense of meaning, which could be critical in helping to maintain abstinence.

Following years of hiatus, research into psychedelic drug treatment has been reinvigorated. Full trials are underway and clearer evidence should become available in the next 5 years.

All of these compounds appear to have low abuse potential, and may have potential uses in addiction treatment. The therapeutic mechanisms of these drugs remain unclear, but anti-depressant effects and stimulation of neuroplasticity are candidates.

The authors declare no competing interests. WL, AM and CJAM receive funding from the Medical Research Council.