Table 2.
Summary of studies using classic and atypical psychedelics for opioid use disorder
| Substance | Author(s) | Year | Study characteristics | Dose | Main findings |
|---|---|---|---|---|---|
| a. Ibogaine | Alper et al. [41] (no access to full paper) | 1999 | Open-label case series | 19.3±6.9 mg/kg | Within 24 h and throughout 72 h, 25/33 cases reported |
| Thirty-three opioid-dependent individuals (DSM-IV) | 1. Resolution of opioid withdrawal | ||||
| 2. No drug-seeking behaviour | |||||
| Other symptom improvements include | |||||
| 1. Drug-seeking behaviour without withdrawal signs (n = 4) | |||||
| 2. Drug abstinence with attenuated withdrawal signs (n = 2) | |||||
| Mash et al. [42] | 2001 | Observational study | Ibogaine HCl: 800 mg (10 mg/kg) | At 12 h, 24 h, and 36 h post-ibogaine treatment, significant reduction in withdrawal symptoms assessed by the “Objective Opiate Withdrawal Scale” and “Opiate-Symptom Checklist” | |
| Thirty-two opioid-dependent (DSM-IV) individuals seeking heroin or methadone detoxification | |||||
| The treatment program offered motivational counselling and referral to aftercare programs and community support groups (twelve-step programs) | |||||
| Noller et al. [43] | 2017 | Observational study | Ibogaine HCl: 31.4±7.6 mg | At 12-month follow-up, there was significant | |
| Fourteen treatment-seeking opioid dependence (DSM-IV) individuals | 1. Attenuation of withdrawal symptoms (ASI Lite) | ||||
| 2. Decrease in drug craving and use (Subjective Opioid Withdrawal Scale) | |||||
| 3. Decrease in depressive symptoms | |||||
| Brown et al. [44] | 2018 | Observational study | Ibogaine HCl: 1,540±920 mg | Significant reduction in opioid withdrawal between pre- and post-treatment with ibogaine | |
| Thirty treatment-seeking opioid-dependent individuals (DSM-IV) | Relative to baseline, at 3-, 6-, 9-, 12-month follow-ups, significant improvement in Drug Use, Family/Social Status, and Legal Status (ASI Lite) | ||||
| Malcolm et al. [45] | 2018 | Observational study | Ibogaine HCl: 18–20 mg/kg | At 48 h post-ibogaine treatment, relative to baseline | |
| Fifty opioid-dependent individuals (DSM-V) with prior ibogaine treatment experience for their opioid dependence | For participants who experience post-acute withdrawal symptoms at 72 h post-ibogaine administration, an additional 1–5 mg/kg ibogaine HCl was administrated | 1. 78% of patients did not experience clinical signs of opioid withdrawal | |||
| Three-part treatment program, including coaching, ibogaine administration, a week-long ibogaine detoxification treatment, and optional residential aftercare program or weekly recovery coaching | 2. 79% reported minimal cravings for opioids | ||||
| 3. 68% reported mild subjective withdrawal symptoms | |||||
| b. Ketamine | Krupitsky et al. [46] | 2002 | Double-blind active-placebo-controlled randomised clinical trial | Hallucinogenic/high dose: 2.0 mg/kg (im) | High dose of ketamine relative to the low dose showed significantly |
| Seventy detoxified heroin dependent patients | Non-hallucinogenic/low dose: 0.2 mg/kg (im) | 1. Greater rate of abstinence within the first 2 years of follow-up | |||
| Existentially oriented psychotherapy in combination with one ketamine session (hallucinogenic dose or sub-hallucinogenic dose active placebo) | 2. Greater and longer-lasting reduction in heroin craving | ||||
| 3. Greater positive change in nonverbal unconscious emotional attitudes | |||||
| 4. Lower relapse rates | |||||
| c. Classic psychedelics | Savage and McCabe [28] | 1973 | Seventy-eight heroin dependent inmates randomly assigned to either a single dose of LSD and psychotherapy or to an outpatient program with weekly psychotherapy sessions (control) | LSD, 300–350 μg | Significantly higher abstinent rates in the LSD-assisted psychotherapy group relative to the control group at 6- and 12-month follow-ups |
| At 12-month follow-up, the LSD group presented with 33% abstinence rates relative to the 5% rate of the control group | |||||
| Pisano et al. [47] | 2017 | Association study | Psilocybin | Psychedelic drug use is associated with | |
| 44,000 responders with history of illicit opioid user who completed the National Survey on Drug Use and Health (NSDUH) from 2008 to 2013 and met NSDUH’s dependence criteria | LSD | 1. 27% reduced risk of past-year opioid dependence | |||
| Mescaline/Peyote/San Pedro | 2. 40% reduced risk of past-year opioid abuse | ||||
| DMT/Ayahuasca | |||||
| Dose N/A | |||||
| Argento et al. [48] | 2022 | Prospective cohort survey study | Classic psychedelics | Significantly reduced odds of subsequent daily opioid use (Adjusted Odds Ratio: 0.45; 95% Confidence Interval: 0.29–0.70) | |
| Cohorts of community-recruited people who use drugs (PWUD) in Vancouver, Canada | Dose N/A | ||||
| Among 3,813 PWUD at baseline, 1,093 (29%) reported daily use of illicit opioids and 229 (6%) reported psychedelic use in the past 6 months |
ASI, Addiction Severity Index; DMT, N, N-dimethyltryptamine; DSM, Diagnostic and Statistical Manual of Mental Disorders; HCl, hydrochloride; LSD, lysergic acid diethylamide; NSDUH, National Survey on Drug Use and Health; PWUD, people who use drugs.