Addiction

Key Insights

• Substance use disorder (SUD) is a complex condition in which people have the inability to stop using a substance like alcohol or tobacco or stop engaging in behaviour despite it causing psychological and physical harm. SUDs shoulder a significant burden of the global disease burden.
• Researchers have been attempting to use psychedelics to treat SUDs since the first wave of psychedelic research in the 1950s and 1960s. Promising research is continuing to take place with various psychedelics and there are many industry players focusing their efforts on different SUDs.

Index of psychedelics for addiction

What is substance use disorder?

Substance use disorder, commonly referred to as addiction, is a complex condition in which there is the uncontrolled use of a substance despite harmful consequences [1].

People with a substance use disorder have the inability to stop using a substance like alcohol, tobacco or illicit drugs, or stop engaging in a behaviour despite it causing psychological and physical harm. Addiction is not limited to substance use and can also involve activities such as gambling, eating or working [2].

People with a substance use disorder may have distorted thinking and behaviours which has been accredited to changes in the brain’s structure and function. As a result of these changes, people often experience intense cravings, changes in personality and other behaviours [1].

Substance use disorder causes people to feel compelled to satisfy their addiction regularly due to cravings and prioritising this above all else. These symptoms/behaviours include spending money they do not have on their addiction, failing to meet obligations in work/other responsibilities, carrying out risky behaviours like driving while intoxicated or spending the majority of their time trying to satisfy their addiction [3].

While symptoms can only be experienced by the person with the disorder, signs which can be observed by other people exist including secretiveness, stealing and changes in their social group, to name a few [4].

It is estimated that over 2% of the world’s population live with some form of substance use disorder and, almost 12 million deaths can be attributed to substance use annually. Moreover, these disorders represent a significant health burden, accounting for 1.5% of the global disease burden as measured in DALYs [5].

Diagnosis & treatment

Diagnosing substance use disorder requires a multidisciplinary approach, involving evaluation and assessment by a psychiatrist, a psychologist or licensed alcohol and drug counsellor [3].

The DSM-V sets out 11 criteria for diagnosing someone with a substance use disorder. Some of these criteria include hazardous use, social/interpersonal problems related to use, withdrawal and physical/psychological problems related to use [6]. A person must meet two or more of these criteria within a 12-month period in order to be diagnosed with a substance use disorder.

A number of instruments have been designed to measure addiction severity such as the Addiction Severity Index (ASI) or the Severity of Dependence Scale (SDS).

Currently, there is no cure for substance use disorder. Treatment is based on individual needs and any related medical or mental health disorders a person may be experiencing.

For substance use disorders, detoxification is often the first point of call. Medically-assisted detox allows a person to rid their body of addictive substances in a safe environment and is especially beneficial to people experiencing withdrawal symptoms [7].

Cognitive Behavioural Therapy (CBT) is another useful tool for a range of addiction disorders as it helps people to recognise their unhealthy behaviours and develop coping skills. Twelve-step therapy (12-steps programs) is another form of useful therapy, with organizations like Alcoholics Anonymous (AA) using this form of therapy.

Depending on the type of substance used in the disorder, a range of medications exist. For alcohol and opioid use disorders, Vivitrol is often used which acts by blocking opioid receptors in the brain, therefore, minimizing the urge to use [8]. A combination of behavioural therapy and medication is often used to treat people with substance use disorders.

Substance use disorder and psychedelics

Research into the potential of psychedelics to treat substance use disorders dates back to the first era of psychedelic research in the 1950s and 1960s. In the 1950s, Humphrey Osmond and his colleagues began treating alcoholics in Canada with LSD and achieved significant rates of recovery [9].

These researchers also engaged with Alcoholics Anonymous groups and co-founder of AA Bill Wilson believed that LSD could help alcoholics achieve a “spiritual awakening and start on the path of recovery [10].”

However, like the majority of psychedelic research from this era, trials were not conducted with methodological rigour and therefore, findings from trials using psychedelics to treat alcoholism were not widely accepted. A comprehensive review of research exploring the positives and negatives of using psychedelics to treat alcoholism during this era can be found here.

Nevertheless, the findings from this era have inspired modern researchers to explore this potential for a range of substance use disorders, using the highest possible standards of modern clinical practice. 

A wide range of psychedelics is currently being trialled in the treatment of various substance use disorders.

Psilocybin

In 2014, Matthew Johnson and his colleagues at Johns Hopkins carried out the first study using psilocybin in tandem with cognitive behavioural therapy (CBT) to treat tobacco addiction. This open-label pilot study (n=15) found that 80% of participants were no longer smoking after six months following a moderate (20mg/70kg) and high (30mg/70kg) dose of psilocybin. Such findings stand in contrast to commonly reported rates of smoking cessation following conventional behavioural and/or pharmacological therapies, which are typically <35%.

A long-term follow-up study of participants in the trial found that 67% of those involved did not return to smoking. This was at 60% at an average of 30-month follow-up.

Further qualitative analysis by Tehseen Noorani and colleagues identified a number of factors that the trial participants accredited to their cessation in smoking behaviours. These factors included vivid insights gained during the psilocybin experience, good preparation, and strong rapport with the study team, to name a few.

While the open-label design of the trial and the small sample does not allow for any definitive conclusions to be drawn, the study has shown that psilocybin may be an effective treatment for substance use disorders and has laid the foundations for future research.

Noteworthily, the team at Johns Hopkins have recently been awarded the first federal grant in over 50 years for psychedelic treatment research and will use the grant to further explore the effects of psilocybin on tobacco addiction.

MDMA

In the world of psychedelics, MDMA is perhaps most well-known for its ability to alleviate the symptoms of PTSD thanks to the work being done at MAPS. However, the therapeutic potential of MDMA may be used to treat other mental health disorders including substance use disorders.

After making a case for utilizing MDMA-assisted therapy for the treatment of alcohol disorder in 2017, Dr Ben Sessa and colleagues carried out the world’s first clinical trial investigating the safety and tolerability of MDMA in patients with alcohol use disorder. 

Published in 2021, this trial found that not only was MDMA well tolerated by participants (n=13), alcohol consumption at nine months post-trial was 18.7 units per week compared to 130.6 units per week before the trial began. While placebo-controlled trials are needed, the findings of this study emphasize the potential of MDMA for substance use disorders.

Ketamine

Some clinical trials have taken place exploring the effects of using ketamine to treat substance use disorders.

Elias Dakwar and the team at Columbia University have conducted two separate trials using intravenously administered ketamine to treat both cocaine dependence and alcohol use disorder.

In the double-blind placebo-controlled trial exploring the effects of ketamine on cocaine dependence plus mindfulness-based therapy, the ketamine group scored significantly better and were 53% less likely to relapse when compared to the midazolam (placebo) group.

A similarly designed study using a single ketamine infusion in tandem with motivational enhancement therapy to treat alcohol use disorder found that ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam.

A study published at the beginning of 2022 assessed the effectiveness of 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education, in people with alcohol use disorder (AUD). It was found that participants in the ketamine groups abstained from alcohol for a significantly longer number of days at 6-month follow-up while the greatest abstinence was in the ketamine plus therapy group. Relapse times did not differ across the four groups. Sponsored by Awakn Life Sciences, this study is the first in the world to explore the effects of ketamine-assisted therapy on AUD.

A review of seven studies investigating the effects of ketamine on different substance use disorders found that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment.

Ibogaine

A number of clinical trials have taken place exploring the potential of ibogaine in treating the symptoms of substance use disorders. Research exploring the anti-addiction properties of ibogaine dates back to the 1990s and many clinics offering ibogaine treatment exist in countries where ibogaine remains somewhat legal such as in Mexico.

A 2017 study, carried out in New Zealand where ibogaine is legal, found a single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months.

An observational study involving people seeking addiction treatment at a private clinic (n=30) found that ibogaine was associated with substantive effects on opioid withdrawal symptoms for up to one month, or even 12 months in select individuals.

While ibogaine may be used to treat other substance use disorders, one of its most significant therapeutic uses lies in the treatment of opioid use disorder. In the U.S alone, over 75,000 overdose deaths were attributed to opioids in 2021 [11]. Notwithstanding, while novel treatments for opioid use disorder are needed, the accompanying adverse effects ibogaine has on cardiotoxicity cannot be understated.

One of the major effects ibogaine has on the cardiovascular system is the prolongation of the QT interval, the time it takes for the heart chamber to contract and subsequently relax, which can increase a person’s risk of cardiac arrhythmia [12]. Subsequently, adequate patient screening is necessary before administering ibogaine as well as strict medical observation during the experience to minimize any potentially fatal risks.

Ayahuasca

Many review articles point to the therapeutic potential of using ayahuasca for treating SUDs. While few randomized-controlled trials have taken place with ayahuasca, a range of survey studies and positive anecdotal reports exist surrounding this psychedelic’s ability to help those with a SUD. These positive benefits largely come from Indigenous populations who use ayahuasca for religious purposes as well as the many people who have travelled to countries like Peru and Colombia where they can take part in ayahuasca ceremonies led by Indigenous groups.

A qualitative interview study (n=32) of members of the Santo Daime Church, who use ayahuasca as a religious sacrament, reported that this population attributed psychological and physical benefits to their ayahuasca use. Moreover, 22 out of the 24 participants who had reported a history of drug or alcohol dependence were said to be in full remission which they attributed to their participation in the church.

This survey study (n=1947) of people attending União do Vegetal (UDV) meetings on substance abuse compared their use of alcohol and tobacco to a national normative sample of Brazilians. While lifetime use of these substances was higher in the UDV-attending groups, the results indicate an association between reduced current alcohol and tobacco use amongst this group who participate in ayahuasca ceremonies.

An interview study (n=11) of members of an Indigenous community in Canada who use ayahuasca to help community members with SUDs found that all participants reported a decrease in substance use and cravings, while eight participants fully ceased using one substance. Participants stated that ayahuasca helped them to recognize negative thought patterns and behaviours related to their substance use.

This cross-sectional survey study (n=8269) investigated associations between ayahuasca consumption in naturalistic settings and the use of alcohol and other drugs across 40 different countries. Ayahuasca use was both strongly and consistently associated with very low (or even abstinence from) drug or alcohol use, with and without prior substance use disorders.

How might psychedelics treat substance use disorders?

Similar to other disorders for which psychedelics hold promise, in substance use disorders, the exact mechanisms are speculative. Their mechanisms of action are largely related to each drug’s specific effects on 5HT-2A or NMDA receptors.

Classic psychedelics like psilocybin are believed to affect the brains’ default mode network (DMN) thereby exerting their therapeutic effects.

The DMN is a collection of neural pathways that govern our self-image, our autobiographical memories, and our deeply ingrained beliefs and thought patterns [13]. 

Aberrant patterns of brain functional connectivity in the DMN have been observed across different classes of substance use disorder and are associated with craving and relapse [14].

Under the influence of psychedelics, activity within the DMN is believed to decrease, allowing people to break free from destructive neural patterns which drive their addictive behaviours and lifestyle.

Ketamine, on the other hand, is an NMDA receptor agonist. By binding to these receptors, ketamine increases the levels of the neurotransmitter glutamate at the synapse.

Ultimately, ketamine promotes neurogenesis and plasticity as well as disrupting neural networks which may block the reconsolidation of drug-related memories [15].

Compared to conventional treatments, psychedelics have been shown to have persisting long-lasting effects on the symptoms of addiction, making them a potentially very useful tool for treating substance use disorders.

Psychedelic industry and addiction

A number of players in the psychedelic industry are attempting to harness the potential of psychedelics for treating substance use disorders.

At Awakn Life Sciences, the aforementioned Ben Sessa, the company’s Chief Medical Officer, and the rest of the team Awakn are exploring the use of psychedelics to treat substance user disorders such as gambling addiction, behavioural addiction, opioid addiction as well as tobacco addiction.

Recently, Awakn announced that they are currently recruiting for the world’s first trial using ketamine to treat gambling addiction. This trial will be led by Celia Morgan at the University of Exeter who also led the aforementioned trial exploring the effects of ketamine-assisted therapy in people with AUD. Moreover, Awakn is developing new chemical entities, synthetic derivatives of other psychedelics, in order to help them tackle substance use disorders.

The team at MindMed are working on using the ibogaine derivative 18-MC (18-Methoxycoronaridine) to treat various forms of addiction. 18-MC has similar outcomes to ibogaine in terms of reducing substance use, however, it has a stronger safety profile in terms of its effects on the cardiovascular system. MindMed has announced that this trial was completed in December 2021 and that the results are due to be published in early 2022.

Other companies active in this space include Universal Ibogaine and Entheon Biomedical.

As the name suggests, Universal Ibogaine is treating persons with addiction disorders using ibogaine. Etheon Biomedical on the other hand is attempting to use DMT to treat addiction, with an animal model study underway in Israel.

Ultimately, novel treatments are needed for substance use disorders. As research in this field of psychedelic science progresses, the use of psychedelics to treat these disorders may soon become a reality.

References

1. American Psychiatric Association. (2020). What is addiction? Washington DC: American Psychiatric Association. https://www.psychiatry.org/patients-families/addiction/what-is-addiction

2. Felman, A. (2021). What is addiction? Medical News Today. https://www.medicalnewstoday.com/articles/323465

3. Mayo Clinic. (2017). Drug addiction (substance use disorder). Rochester: Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/drug-addiction/symptoms-causes/syc-20365112

4. Hartney, E. (2020). Signs and Symptoms of Addiction. Verywell Mind. https://www.verywellmind.com/symptoms-of-addiction-22244

5. Ritchie, H., & Roser, M. (2019). Drug Use. Our World in Data. https://ourworldindata.org/drug-use#disease-burden-from-substance-use-disorders

6. Hartney, E. (2020). The 11 Official Criteria for Addiction/Substance Use Disorder. Verywell Mind. https://www.verywellmind.com/what-are-the-official-criteria-for-addiction-22493

7. Underwood, C. (2020). 6 Treatments For Addiction That Are Proven Successful. WebMD. https://www.webmd.com/connect-to-care/addiction-treatment-recovery/successful-treatments-for-addiction

8. National Institute of Drug Abuse. (2014). Addiction Medications. National Institute of Drug Abuse. https://web.archive.org/web/20220121080920/http://www.drugabuse.gov/publications/principles-adolescent-substance-use-disorder-treatment-research-based-guide/evidence-based-approaches-to-treating-adolescent-substance-use-disorders/addiction-medications

9. Dyck, E. (2006). ‘Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism, 1950–1970. Social History of Medicine, 313-329. https://academic.oup.com/shm/article-abstract/19/2/313/2259116

10. Hill, A. (2012). LSD could help alcoholics stop drinking, AA founder believed. London: The Guardian. https://www.theguardian.com/science/2012/aug/23/lsd-help-alcoholics-theory

11. Centers for Disease Control and Prevention. (2021). Drug Overdose Deaths in the U.S. Top 100,000 Annually. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm

12. Koenig, X., & Hilber, K. (2015). The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation. Molecules.

13. Buckner, R., Andrews-Hanna, J., & Schacter, D. (2008). The brain’s default network: anatomy, function, and relevance to disease. Annals of The New York Academy of Sciences. https://pubmed.ncbi.nlm.nih.gov/18400922/

14. Zhang, R., & Volkow, N. (2019). Brain default-mode network dysfunction in addiction. Journal of Neuroimaging. https://www.researchgate.net/publication/333920984_Brain_default-mode_network_dysfunction_in_addiction

15. Ezquerra-Romano, I., Lawn, W., Krupitsky, E., & Morgan, C. (2018). Ketamine for the treatment of addiction: Evidence and potential mechanisms. Neuropharmacology, 72-82. doi:https://doi.org/10.1016/j.neuropharm.2018.01.017