Table 1.
Summary of studies using classic and atypical psychedelics in non-ceremonial and ceremonial settings for alcohol use disorder
| Substance | Author(s) | Year | Study characteristics | Drug and dose | Main findings |
|---|---|---|---|---|---|
| a. Classic psychedelics (psilocybin, LSD) | Krebs et al. [27] | 2012 | Meta-analysis of randomised controlled trials | LSD | Significantly beneficial short-term (2–3-month post-treatment) and medium-term (6-month post-treatment) effects of LSD on alcohol misuse |
| Six eligible trials | Single dose | 3/6 trials reported maintained abstinence from alcohol at short-term follow-up | |||
| Total of 536 treatment-seeking participants (LSD, n = 325; placebo, n = 211) | Doses range from 3 μg/kg (∼210 μg) to 800 μg | ||||
| Trials included treatment programs varying from individual or group psychotherapy, interpersonal skills training, and counselling on alcohol misuse and withdrawal | |||||
| Bogenschutz et al. [29] | 2015 | Single-group within-subject proof-of-concept study | Psilocybin | PHDD and percent of drinking days decreased post psilocybin (weeks 5–12) relative to baseline and weeks 1–4 (therapy only) | |
| Ten volunteers with alcohol dependence (DSM-IV) with at least two heavy drinking days in the past 30 days | Session 1: 0.3 mg/kg | Abstinence increased significantly following psilocybin administration relative to weeks 1–4 (therapy only) | |||
| 12-week MET with two psilocybin sessions (at 4 and 8 weeks) | Session 2: 0.4 mg/kg | Gains were largely maintained at follow-up to 36 weeks | |||
| Intensity of acute effects in the first psilocybin session (week 4) strongly predicted change in | |||||
| 1. Drinking during weeks 5–8 | |||||
| 2. Increases in abstinence | |||||
| 3. Decreases in craving | |||||
| 4. Changes in self-efficacy during week 5 | |||||
| Garcia-Romeu et al. [30] | 2019 | Retrospective cross-sectional online survey study | Psilocybin | Following the reference psychedelic experience | |
| 343 individuals fulfilling DSM-V criteria for past or current AUD | LSD | 1. 83% no longer met AUD criteria | |||
| DMT/Ayahuasca | 2. 28% endorsed psychedelic-associated changes in life priorities/values facilitating reduced alcohol misuse | ||||
| Moderate to high doses | 3. 69% reported less severe withdrawal symptoms, particularly craving | ||||
| Bogenschutz et al. [31] | 2022 | Double-blind randomised clinical trial | Psilocybin versus diphenhydramine (placebo) | PHDD during the 32-week double-blind period was 9.7% (robust and sustained decreases in drinking) for the psilocybin group and 23.6% for the diphenhydramine group | |
| Ninety-five adults aged 25–65 years with a diagnosis of alcohol dependence (DSM-IV) and at least 4 heavy drinking days during the 30 days prior to screening | Session 1: 25 mg/70 kg versus 50 mg | Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group | |||
| 12 weeks of manualised psychotherapy (MET and cognitive behavioural therapy) and were randomly assigned to receive psilocybin or diphenhydramine twice (at 4 and 8 weeks) | Session 2: 25–40 mg/70 kg versus 100 mg | There were no serious adverse events among participants who received psilocybin | |||
| Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy | |||||
| Participants who were treated with psilocybin were more likely than those receiving diphenhydramine to have no heavy drinking days | |||||
| b. Atypical psychedelics (ketamine, ibogaine, 5-MeO-DMT, MDMA) | Krupitsky et al. [32] (no access to full paper) | 1992 | Non-randomised transpersonal therapy approaches with elements of aversive therapy in combination with one ketamine session | Ketamine | Ketamine-assisted therapy promoted higher levels of abstinence compared to the control group |
| One hundred eighty-six alcohol-dependent individuals who either underwent ketamine assisted therapy or underwent traditional methods of therapy | 2.5 mg/kg (im) | ||||
| Krupitsky and Grinenko [33] (no access to full paper) | 1997 | Transpersonal assisted therapy in combination with one ketamine session | Ketamine | 65.8% abstinence (>1 year) in the ketamine group compared to 24% in the control group | |
| Two hundred eleven recently detoxified alcohol-dependent individuals who either underwent ketamine-assisted therapy or were treated as usual | 2.5 mg/kg (im) | ||||
| Barsuglia et al. [34] | 2018 | Case report of a 31-year-old male military veteran with moderate AUD | Ibogaine | Alcohol cessation and reduced cravings at 5 days post-treatment | |
| Used ibogaine HCl on day 1 and vaporised 5-MeO-DMT on day 3 | 5-MeO-DMT | Effects were sustained at 1 month | |||
| Individual received SPECT neuroimaging before and 3 days after completion of the program | Ibogaine HCl: 1,550 mg (17.9 mg/kg) | Partial return to mild alcohol use at 2 months | |||
| 5-MeO-DMT: 5–7 mg (from 50 mg bufotoxin) | |||||
| Das et al. [35] | 2019 | Randomised single-blind placebo-controlled trial | Ketamine | In the ketamine administration immediately followed by MRM relative to the ketamine alone and MRM retrieval alone conditions, significant decreases were found in the following: | |
| Ninety beer-preferring non-treatment-seeking individuals with problematic alcohol use, no formal AUD diagnosis, and scores >8 in the AUDIT were randomised to one of three conditions | Ketamine HCl and placebo concentrations were maintained at 350 ng/mL for 30 min | 1. Drinking volume | |||
| 1. Ketamine and MRM retrieval with beer | 2. Drinking enjoyment | ||||
| 2. Ketamine alone with orange juice | 3. Urge to drink a beer placed in front of them | ||||
| 3. Placebo and MRM retrieval | 4. General alcohol consumption (beer, wine, or spirits) | ||||
| Dakwar et al. [36] | 2020 | Randomised midazolam-controlled pilot study | Ketamine | Ketamine relative to midazolam significantly | |
| Forty treatment-seeking alcohol-dependent (DSM-IV) individuals | Ketamine HCl: 0.71 mg/kg (iv) | 1. Increased the likelihood of abstinence | |||
| 5-week MET and were randomly assigned to receive ketamine or active control midazolam during week 2 | Midazolam) active control): 0.025 mg/kg | 2. Delayed the time to relapse | |||
| 3. Reduced the likelihood of heavy drinking days | |||||
| Sessa et al. [37] | 2021 | Open-label safety and tolerability proof-of-concept study | MDMA | MDMA treatment was safe and tolerated by all participant | |
| Fourteen detoxification-seeking individuals with AUD (DSM-V) completed a community alcohol detoxification and received an 8-week/10-session course of recovery-based therapy with MDMA at sessions 3 and 7 | Total of 187.5 mg in each session: 125 mg initial dose and 62.5 mg booster dose on same day | Psychosocial functioning improved across the cohort | |||
| At 9-month post-detox, there was a decrease in average units of alcohol consumption by participants from 130.6 units/week pre-detox to 18.7 units/week post-detox | |||||
| Grabski et al. [38] | 2022 | Double-blind placebo-controlled phase II clinical trial | Ketamine | Significantly greater number of abstinence days from alcohol in the ketamine relative to the placebo group at 3- and 6-month follow-up (pooled across therapy conditions) | |
| Ninety-six recently detoxified individuals with AUD (DSM-IV/V) were randomised to one of four conditions | Ketamine: 0.8 mg/kg (iv) | No difference in relapse rates between the ketamine and the placebo groups | |||
| 1. Three weekly ketamine (active) infusions plus psychological therapy (MBRP) (active) | Placebo: 0.9% saline (iv) | ||||
| 2. Three ketamine (active) infusions plus alcohol education (control) | |||||
| 3. Three saline infusions (control) plus psychological therapy (active) | |||||
| 4. Three saline infusions (control) plus alcohol education (control) | |||||
| c. Ceremonial psychedelic use (mescaline-containing Peyote cactus, DMT-containing Ayahuasca brew) | Albaugh and Anderson [39] | 1974 | American Indians from the Cheyenne and Arapaho tribes with alcohol dependence | Peyote cactus | Discussion about alcoholism and emotions during the NAC ceremonies was helpful in overcoming their alcohol dependence |
| 30-day inpatient programme at the Clinton Indian Hospital in Oklahoma | Peyote buttons (average: 11 buttons, 45 mg mescaline each) | Carry-over effect of 7–10 days post peyote of openness and willingness to communicate | |||
| Therapeutic approach: group meetings, cultural and occupational therapy, and taking part in meetings at the Native American Church (NAC), with and without peyote/mescaline | Average mescaline: 500 mg | ||||
| Doering-Silveira et al. [40] | 2005 | Cross-sectional study | Ayahuasca | Significantly lower alcohol consumption in | |
| Eighty-four ayahuasca consuming and national normative sample of adolescents (15–19 years; Brazil) | N/A | 1. Last-month | |||
| Ayahuasca-consuming adolescents (ritual context; n = 41) were selected from three syncretic churches Uniao do Vegetal (UDV) | 2. Last-year | ||||
| Focussing on general drug and alcohol consumption (no addiction) | |||||
| Drunk ayahuasca within a ritual context at least 24 times during the last 2 years prior to the assessment | |||||
| World Health Organisation (WHO) criteria for psychoactive drug use |
ASI, Addiction Severity Index; AUD, alcohol use disorder; AUDIT, Alcohol Use Disorders Identification Test; DMT, N, N-dimethyltryptamine; DSM, Diagnostic and Statistical Manual of Mental Disorders; HCl, hydrochloride; LSD, lysergic acid diethylamide; MDMA, 3,4-methylenedioxymethamphetamine; MET, motivational enhancement therapy; MRM, Maladaptive reward memory; NAC, Native American Church; PHDD, percentage of heavy drinking days; UDV, Uniao do Vegetal (churches); WHO, World Health Organisation; 5-MeO-DMT, O-methyl-bufotenin; MBRP, mindfulness-based relapse prevention.