Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Calleja‐Conde, Javier; Morales-García, José A.; Echeverry‐Alzate, Víctor; Bühler, Kora-Mareen; Giné, Elena; López-Moreno, José Antonio

doi:10.1111/adb.13229

Cited by 23 publications

(17 citation statements)

References 102 publications

(166 reference statements)

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“…Serotonergic psychedelics, in general, have been demonstrated to be potential candidates for the treatment of alcohol dependence. A systematic review including 20 human studies and 7 preclinical studies demonstrates overall promising data for psychedelics to effectively treat the symptoms of AUD, and the psilocybin was specifically demonstrated to be the most consistent compound [ 135 ]. The double-blind clinical trial for the treatment of AUD with psilocybin conducted by Bogenschutz et al (NCT identifier number: NCT02061293) demonstrated the most convincing results so far, helping to consider proceeding with a phase 3 clinical trial.…”

Section: Future Directions and Therapeutic Implicationsmentioning

confidence: 99%

Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism

Domanegg

Sommer

Meinhardt

2023

Cells

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Alcohol abuse is a leading risk factor for the public health burden worldwide. Approved pharmacotherapies have demonstrated limited effectiveness over the last few decades in treating alcohol use disorders (AUD). New therapeutic approaches are therefore urgently needed. Historical and recent clinical trials using psychedelics in conjunction with psychotherapy demonstrated encouraging results in reducing heavy drinking in AUD patients, with psilocybin being the most promising candidate. While psychedelics are known to induce changes in gene expression and neuroplasticity, we still lack crucial information about how this specifically counteracts the alterations that occur in neuronal circuits throughout the course of addiction. This review synthesizes well-established knowledge from addiction research about pathophysiological mechanisms related to the metabotropic glutamate receptor 2 (mGlu2), with findings and theories on how mGlu2 connects to the major signaling pathways induced by psychedelics via serotonin 2A receptors (2AR). We provide literature evidence that mGlu2 and 2AR are able to regulate each other’s downstream signaling pathways, either through monovalent crosstalk or through the formation of a 2AR-mGlu2 heteromer, and highlight epigenetic mechanisms by which 2ARs can modulate mGlu2 expression. Lastly, we discuss how these pathways might be targeted therapeutically to restore mGlu2 function in AUD patients, thereby reducing the propensity to relapse.

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Section: Future Directions and Therapeutic Implicationsmentioning

confidence: 99%

Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism

Domanegg

Sommer

Meinhardt

2023

Cells

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“…In indigenous and neoshamanic contexts, ayahuasca, a botanical decoction originating from the Amazonian rainforest, has been routinely used in the treatment of addictions (Talin and Sanabria, 2017). A systematic review by Calleja-Conde et al pointed to significant benefits in both animal and human studies (Calleja-Conde et al, 2022). Reviews by Frecska et al and James et al discussed additional aspects (Frecska et al, 2016;James et al, 2022).…”

Section: Ayahuascamentioning

confidence: 99%

MDMA, Internal Family Systems therapy, and the Minnesota model in the resolution of C-PTSD-induced alcohol and diazepam addiction—A retrospective case study

Turkia¹

2023

Preprint

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In February 2023, Australia became the first country in the world to allow psychiatrists to prescribe 3,4-methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD). This may have left interested clinicians looking for practical examples of the use of MDMA. In the 1950s and 1960s, psychedelics were successfully utilized in the treatment of alcoholism. This case study, the first of its kind in recent years, illustrates in detail how and why MDMA, combined with Internal Family Systems therapy (IFS), can promote abstinence. The case features a man in his forties with a long history of addiction to alcohol and diazepam. The addiction appeared as an attempt to avoid emotional pain caused by witnessing severe, chronic domestic violence in early childhood perpetrated by an alcoholic stepfather. While alcohol temporarily suppressed complex post-traumatic stress disorder (C-PTSD)-related anxiety, it also created intolerable shame and a feeling of inadequacy, which in turn resulted in increased use of alcohol. SSRI medications initially helped somewhat but failed to resolve the issues in the long term. C-PTSD presented itself not only as anxiety and depression but also as physical tensions and pains, and their relaxation with various substances caused intense pleasure, leading to addiction. Later, diazepam was prescribed as a substitute for alcohol. While alcohol use was reduced, an addiction to diazepam emerged instead. There appeared to be a lack of understanding about the causal relationship between adverse childhood experiences (ACEs) and the addiction, as well as the severity of the condition. Eventually, after several failed attempts at quitting and a suicidal period, the patient accepted that he needed more intensive external help, enrolled in a 28-day retreat utilizing the Minnesota abstinence model, felt unprecedented safety and acceptance, gained insight about the ACEs as a cause of his alcoholism, and was able to give up alcohol and diazepam, but the abstinence was fragile and stressful to maintain. Regardless, 'the most painful issues' caused by witnessing life-threatening domestic violence remained unresolved. A single session combining MDMA and IFS therapy allowed him to safely re-experience these events in an embodied manner. A later IFS session without MDMA complemented the outcome of resolving his C-PTSD and stabilizing his abstinence. (Initial version: January 5, 2023; https://doi.org/10.13140/RG.2.2.31521.48480)

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“…Recent years have seen a resurgence in psychedelic research, a development sometimes referred to as the psychedelic renaissance. Since 2016, three systematic reviews have been conducted evaluating the efficacy of psychedelics (i.e., psilocybin, but also other classic serotonergic psychedelics such as LSD were included in these systematic reviews) as a treatment for psychiatric disorders (i.e., SUD, but also other psychiatric disorders such as depression and anxiety were included in these systematic reviews) ( 19 – 21 ). Although these reviews provide an excellent overview of clinical trials published in the last 25 years, including multiple psychedelics and conditions, they may have missed clinical trials evaluating the efficacy of psychedelics that were conducted before the 1980s ( 19 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…Since 2016, three systematic reviews have been conducted evaluating the efficacy of psychedelics (i.e., psilocybin, but also other classic serotonergic psychedelics such as LSD were included in these systematic reviews) as a treatment for psychiatric disorders (i.e., SUD, but also other psychiatric disorders such as depression and anxiety were included in these systematic reviews) ( 19 – 21 ). Although these reviews provide an excellent overview of clinical trials published in the last 25 years, including multiple psychedelics and conditions, they may have missed clinical trials evaluating the efficacy of psychedelics that were conducted before the 1980s ( 19 – 21 ). As shown by Fuentes et al ( 6 ), many trials have been conducted assessing the efficacy of LSD in SUD in these early decades, which may have been an important era for psilocybin research as well ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of psilocybin in addiction: A systematic review

et al. 2023

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BackgroundPsychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy.MethodsA systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin.ResultsA total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to n = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study (n = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5–12 (mean difference of 26.0, 95% CI = 8.7–43.2, p = 0.008). In another single-arm study (n = 31), 32% (10/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, n = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0–24.7, p = 0.01). In a pilot study (n = 15), the 7-day point prevalence of smoking abstinence at 26 weeks was 80% (12/15), and at 52 weeks 67% (10/15).ConclusionOnly one RCT and three small clinical trials were identified assessing the efficacy of psilocybin combined with some form of psychotherapy in patients with alcohol and tobacco use disorder. All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate whether psilocybin-assisted therapy is effective in patients with SUD.

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Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Cited by 23 publications

References 102 publications

Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism

Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism

MDMA, Internal Family Systems therapy, and the Minnesota model in the resolution of C-PTSD-induced alcohol and diazepam addiction—A retrospective case study

Therapeutic effect of psilocybin in addiction: A systematic review

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