PSYCHEDELICS AS EXIT DRUGS

Some things have to be discovered over and over again or there simply won't be enough research to do. Krebs and Johansen (2012) pooled six studies of lysergic acid diethylamide (LSD) in the treatment of alcoholism from 1966 to 1970:

"In a post hoc analysis of trials with available dichotomized data, we calculated the pooled benefit difference on improvement in alcohol misuse at first follow-up and also calculated the number needed to treat. The benefit difference (also known as the risk difference) for each trial is the percentage of improved patients in the LSD group minus the percentage of improved patients in the control group. The number needed to treat is the inverse of the pooled benefit difference and provides an estimate of the average number of patients needed to be treated with LSD rather than without LSD to achieve one additional patient with improved outcome on alcohol misuse."

That number, they found, was six.

"The pooled odds ratio on improvement in alcohol misuse between the LSD and control groups was 1.96 (95% CI, 1.362.84; p =0.0003) at the first reported follow-up, see Figure 2. Among the five trials with dichotomized data, 185 of 315 (59%) LSD patients and 73 of 191 (38%) control patients were improved at the first reported follow-up, and the pooled benefit difference was 16% (95% CI, 8%−25%; p = 0.0003), or, equivalently, the number needed to treat is six."
https://www.ntnu.edu/documents/139226/8932977/JOP439253.pdf [5609]

Jensen et al (2024) have discovered, all over again, what the LSD researchers found out in the 1950s.

"This open-label, single-group study investigated single-dose psilocybin therapy in ten treatment-seeking adults (eight men and two women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg), and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed with a linear mixed model.

"Results
Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14-59 g/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI, -61.1, -13.9, p = 0.005), and drinks per day decreased by 3.4 units (95% CI: -6.5, -0.3), p = 0.035). This was corroborated by reports of rapid and sustained reductions in craving and increases in selfefficacy.

"Conclusions
Despite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted."
https://www.researchgate.net/publication/383382218_Single-Dose_Psilocybin_Therapy_for_Alcohol_Use_Disorder_Pharmacokinetics_Feasibility_Safety_and_Efficacy_in_an_Open-Label_Study/fulltext/66ca05b897265406eaaa61ea/Single-Dose-Psilocybin-Therapy-for-Alcohol-Use-Disorder-Pharmacokinetics-Feasibility-Safety-and-Efficacy-in-an-Open-Label-Study.pdf?_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6InB1YmxpY2F0aW9uIiwicGFnZSI6InB1YmxpY2F0aW9uIn19 [3481]

Lodetti et al also made the same rediscovery in 2024:

"Alcohol is a harmful drug, and reducing its consumption is a significant challenge for users. Furthermore, alcohol dependence is often treatment-resistant, and no completely effective treatment model is available for chemical dependence. Classic psychedelics, such as LSD, psilocybin, and ayahuasca have been used in different clinical and pre-clinical trials, demonstrating promising pharmacotherapeutic effects in the treatment of treatment-resistant psychopathological conditions, such as addiction, especially related to alcohol dependence. In this work, we conducted a narrative review of the emerging research regarding the potential of psychedelics for alcohol use disorder treatment. Psychedelic substances have demonstrated potential for treating drug addiction, especially AUD, mostly by modulating neuroplasticity in the brain. Given that serotonergic psychedelics do not produce physical dependence or withdrawal symptoms with repeated use, they may be considered promising treatment options for managing drug use disorders. However, certain limitations could be found. Although many participants achieve positive results with only one treatment dose in clinical studies, great inter-individual variability exists in the duration of these effects. Therefore, further studies using different doses and experimental protocols should be conducted to enhance evidence about psychedelic substances."
https://www.sciencedirect.com/science/article/abs/pii/S0278584624001970 [3482]

And de Jonge et al (2024) discover in "Psychedelic Research for Alcohol Use Disorder with Comorbid Major Depressive Disorder: An Unmet Need"

"In AUD, a growing evidence base for psilocybin treatment shows a promising beneficial and sustained effect on measures of drinking frequency. In MDD [major depressive disorder], a recent meta-analysis has demonstrated that psilocybin therapy provides a large and consistent reduction in depressive symptoms compared to no treatment. Co-occurrence of MDD and AUD is quite prevalent, and this comorbidity exacerbates symptomatology of the two individual disorders and complicates their treatment."
https://link.springer.com/article/10.1007/s11920-024-01567-4 [3772]

In "The Relationship Between Psychedelic Use and Alcohol Use Disorder in a Nationally Representative Sample" of 139,524 individuals, Zech et al (2025) lump LSD, MDMA and ketamine together under a dubious "psychedelics" head, but only LSD was significantly associated with reduced alcohol consumption:

"Past-year LSD use was significantly associated with lower odds of AUD (adjusted odds ratio [aOR] = 0.70, p = .006). However, use of MDMA (aOR = 1.17, p = .229) and ketamine (aOR = 1.28, p = .235) was not associated with AUD. In a quasi-Poisson regression analysis, past-year LSD use was found to be associated with 15.7% fewer AUD symptoms (IRR = 0.84, 95% CI: 0.72 - 0.98, p = .033), but neither past-year MDMA nor past-year ketamine use were significantly associated with AUD symptoms (MDMA: IRR = 0.97, 95% CI: 0.83 - 1.13, p = .731; ketamine: IRR = 1.21, 95% CI: 0.93 - 1.57, p = .139). Taken together, these findings indicate differential associations between specific psychedelics and AUD, with LSD use linked to a reduced risk of AUD."
https://pubmed.ncbi.nlm.nih.gov/41208129/ [5624]

In an article for Deutsches rzteblatt international, Spangemacher et al (2024) feel that psychotherapy's embrace of psilocybin (although the Defendant believes this idea misses the point) is a first for psychiatry:

"This review is based on pertinent publications (since 1969) that were retrieved by a selective search carried out in August 2024 in the PubMed and ScienceDirect databases employing the keywords 'psilocybin' AND 'long-term effects' AND 'mental disorders', with an emphasis on randomized, controlled clinical trials (RCTs).

"Results: The available RCTs document the efficacy of psilocybin mainly against depression, including otherwise medically refratory depression. Most of the trials revealed a strong effect, with Cohens d ranging from 0.67 to 2.6; they used a variety of depression scales and follow-up intervals. Evidence was also found for the efficacy of psilocybin against substance use disorders (alcohol in particular) and symptoms of anxiety accompanying life-threatening somatic illnesses, such as cancer. Initial uncontrolled studies have also shown significant improvement after the administration of psilocybin for other indications.

"Conclusion: Treatment with psilocybin differs fundamentally from classic psychopharmacotherapy. Its potentially transdiagnostic, rapid, and sustainable efficacy and its positive effect on further dimensions of mental health beyond the patients symptoms and psychopathology imply that it may have disease modifying and salutogenic mechanisms of action. Psychotherapy accompanied by the administration of psychedelic drugs may turn out to be the first disease-modifying treatment in the history of psychiatry."
https://www.researchgate.net/profile/Moritz-Spangemacher/publication/387461413_Psilocybin_as_a_Disease-Modifying_Drug-a_Salutogenic_Approach_in_Psychiatry/links/67af66a8207c0c20fa8a2495/Psilocybin-as-a-Disease-Modifying-Drug-a-Salutogenic-Approach-in-Psychiatry.pdf?_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6InB1YmxpY2F0aW9uIiwicGFnZSI6InB1YmxpY2F0aW9uIn19 [4840]

As Keighley et al (2025) explained all over again in "A Systematic Review and Meta-Analysis Investigating the Efficacy of Various Psychedelic Drugs for the Treatment of Substance Use Disorder":

"Lysergic Acid Diethylamide has low toxicity and abuse potential and is a serotonergic hallucinogen that works as a 5-HT2A agonist. Researchers used LSD to treat alcoholism throughout the middle to late 20th century. A meta-analysis conducted in 2012 by [Krebs and Johansen] assessed the meaningful effects of LSD in aid for alcoholism from six randomised trials. Across six studies, 325 participants were randomly assigned to receive a dose of LSD, and 211 participants were assigned to a control condition. Results demonstrated the effectiveness of LSD on alcohol misuse for up to six months."

Apparently even taking LSD in prison can help:

"A research study conducted in the 1970s administered LSD to reduce substance misuse in heroin addicts. Seventy-eight inmates from a correctional facility were randomly assigned to a treatment (n = 37) or control group (n = 37). The treatment group was administered one dose of LSD-assisted psychotherapy and the control group were undertaking weekly group psychotherapy with no psychedelic administration. The LSD group displayed significantly higher abstinence outcomes at both the 06-month and 712-month follow-up compared to the control group.

...

"Moreover, an anonymous online survey by Garcia-Romeu et al. 2020 assessed individuals reduced SM following psychedelic intake. Of the 444 respondents, 96% of individuals met the criteria for an SUD and 79% for a severe SUD. Individuals reported taking a moderate to high dose of LSD (43%), psilocybin (29%), or other (28%). Following psychedelic encounters, only 27% met the criteria for an SUD. The most significant reductions in SM were associated with those who reported a highly personal experience."

In the face of all the financial motivations, the authors note in their findings that:

"We also found a non-significant difference between the effectiveness of psychedelic treatment paired with psychotherapy and psychedelic treatment alone."
https://www.mdpi.com/2227-9032/13/21/2668 [5634]

It's just as well. One apparently unnoticed problem with treating alcoholics with LSD is that most of them have already spent all their money on alcohol - so will be unable to fund Slovenia's psychiatric lifestyles in the hope that someone else will fix their problem.

"In New Zealand...

"A clinical study using mushrooms containing the psychoactive psilocybin to treat methamphetamine addiction has just completed its first phase of trials.

"Over the past month the first cohort of participants have undergone sessions at Rangiwaho Marae south of Gisborne.

"Jody Toroa, a trustee at Rangiwaho Marae, said the goal of the study is find a way to care for whžnau in the grips of meth addiction, mental illness and PTSD."
https://www.rnz.co.nz/news/te-manu-korihi/539320/marae-based-study-into-psychoactive-mushroom-for-treating-methamphetamine-addiction-completes-first-phase-of-trials [3946]

In "Psilocybin-Assisted Psychotherapy for Methamphetamine Use Disorder: A Pilot Open-Label Safety and Feasibility Study" by Knock et al (2025):

"Fourteen participants completed the study intervention and 13 completed 90-day post-dose follow-up. No serious adverse events (AEs) occurred, and the seven treatment related AEs were self-limiting and mild to moderate in severity. AEs included hypertension during the dosing session and headache (n=4), nausea (n=1) and noise sensitivity (n=1) within the week following the dose. Methamphetamine use (over the prior 28 days) decreased from screening (median 12 days, IQR 7-16, n=15) to day 28 (median 0 days, IQR 0-2, n=13) and 90 (median 2 days, IQR 1-4, n=14) post psilocybin. Methamphetamine craving decreased while quality of life, depression, anxiety, and stress improved from baseline to day 28 and 90 follow-up.

"Interpretation
Psilocybin assisted psychotherapy for methamphetamine use disorder was feasible to implement in an outpatient setting, did not appear to generate safety concerns, and demonstrated signals of effectiveness warranting further investigation."
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5116026 [5443]

Reviewing a decade of discoveries which existed long before these discoveries were made in "The Therapeutic Potential of Psychedelics in Treating Substance Use Disorders: A Review of Clinical Trials" Hogea et al (2025) report:

"Our results highlight the key findings from 16 clinical trials investigating psychedelic therapy for SUDs. Psychedelics like psilocybin and ayahuasca showed promise in reducing alcohol and tobacco dependence, with psilocybin being particularly effective in decreasing cravings and promoting long-term abstinence. The studies revealed significant improvements in substance use reduction, especially when combined with psychotherapy. However, the variability in dosages and study design calls for more standardized approaches. These findings emphasize the potential of psychedelics in SUD treatment, though further large-scale research is needed to validate these results and develop consistent protocols. Conclusions: This research reviewed the past decades international experience, emphasizing the growing potential of psychedelic therapy in treating SUDs pertaining to alcohol, tobacco, and cocaine dependence. Psychedelics such as psilocybin and ketamine can reduce cravings and promote psychological well-being, especially when combined with psychotherapy. However, regulatory barriers and specialized clinical training are necessary to integrate these therapies into mainstream addiction treatment safely. Psychedelics offer a promising alternative for those unresponsive to conventional methods."

https://www.mdpi.com/1648-9144/61/2/278 [5103]

For tobacco addicts, smoking cessation with a single dose of psilocybin was superior to nicotine patches.

In a randomized clinical trial by Johnson et al (2026) and published in Substance Use and Addiction, 42 participants randomized to receive psilocybin had more than 6 times greater odds of prolonged smoking abstinence 6 months after treatment than 40 participants who received the nicotine patch.

"A total of 82 psychiatrically healthy adult smokers (mean [SD] age, 47.6 [12.0] years; 49 [59.8%] male) participated in the study, with 68 (82.9%) completing the 6-month follow-up. At 6-month follow-up, 17 participants receiving psilocybin (40.5%) exhibited biochemically verified prolonged abstinence compared with 4 participants using the nicotine patch (10.0%) (odds ratio, 6.12; 95% CI, 1.99-23.26; P = .003), and 22 participants receiving psilocybin (52.4%) exhibited biochemically verified 7-day point prevalence abstinence compared with 10 participants using the nicotine patch (25.0%) (odds ratio, 3.30; 95% CI, 1.32-8.70; P = .01). No serious adverse events were attributed to psilocybin or nicotine patch."

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2846155 [6011]

According to "The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis

""The findings from this meta-analysis reinforce the growing consensus that the intensity of psychedelic-induced subjective experiences plays a pivotal role in mediating therapeutic outcomes across a wide range of psychiatric and substance use disorders."

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