Associations between cannabis policies and state-level specialty cannabis use disorder treatment in the United States, 2004-2019.

BACKGROUND: Cannabis use disorder (CUD) treatment prevalence decreased in the US between 2002 and 2019, yet structural mechanisms for this decrease are poorly understood. We tested associations between cannabis laws becoming effective and self-reported CUD treatment. METHODS: Restricted-use 2004-2019 National Surveys on Drug Use and Health included people ages 12+ classified as needing CUD treatment (i.e., past-year DSM-5-proxy CUD or last/current specialty treatment for cannabis). Time-varying indicators of medical cannabis laws (MCL) with/without cannabis dispensary provisions differentiated state-years before/after laws using effective dates. Multi-level logistic regressions with random state intercepts estimated individual- and state-adjusted CUD treatment odds by MCLs and model-based changes in specialty CUD treatment state-level prevalence. Secondary analyses tested associations between CUD treatment and MCL or recreational cannabis laws (RCL). RESULTS: Using a broad treatment need sample definition in 2004-2014, specialty CUD treatment prevalence decreased by 1.35 (95 % CI = -2.51, -0.18) points after MCL without dispensaries and by 2.15 points (95 % CI = -3.29, -1.00) after MCL with dispensaries provisions became effective, compared to before MCL. Among people with CUD in 2004-2014, specialty treatment decreased only in MCL states with dispensary provisions (aPD = -0.91, 95 % CI = -1.68, -0.13). MCL were not associated with CUD treatment use in 2015-2019. RCL were associated with lower CUD treatment among people classified as needing CUD treatment, but not among people with past-year CUD. CONCLUSIONS: Policy-related reductions in specialty CUD treatment were concentrated in states with cannabis dispensary provisions in 2004-2014, but not 2015-2019, and partly driven by reductions among people without past-year CUD. Other mechanisms (e.g., CUD symptom identification, criminal-legal referrals) could contribute to decreasing treatment trends.

Psychedelics in Psychiatry, the Nursing Influence, and the Future of Psychedelic Therapies.

OBJECTIVE: Psychedelics and psychedelic-assisted therapies (PATs) are on the cusp of becoming medicalized treatment modalities within the United States, both as potential U.S. Food and Drug Administration (FDA)-approved treatment and therapeutic options outside the medical model, through decriminalization efforts within individual states. Bringing with it a paradigm shift in the delivery of health care for both physical and mental health treatment. A workforce of highly trained facilitators will be needed to meet the anticipated demand for this type of treatment and nurses can play a key role in meeting this demand. This article serves to introduce psychedelic-assisted therapies to psychiatric-mental health nurses as we start to see this new field emerge. METHOD: Review of published literature and other media. RESULTS: Results based on historical data, modern applications, and future considerations. CONCLUSIONS: Nurses have been involved with psychedelic-assisted therapies in the past and are fully capable of providing a wide range of roles upon the anticipated approval as a treatment modality.

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions. However, these medications are limited in their efficacy for treating PTSD-AUD comorbidity. Emerging research on the nonclassical psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) suggests that it may be an effective drug used in conjunction with psychotherapy. The following reviews the current research for clinical pharmacotherapies, as well as MDMA-integrative psychotherapy as they pertain to PTSD and AUD in isolation and co-occurrence. Future directions for the role of psychedelic-integrative therapy for the treatment of this comorbidity are discussed.

Mindfulness meditation and psychedelics: potential synergies and commonalities.

There has been increasing scientific and clinical interest in studying psychedelic and meditation-based interventions in recent years, both in the context of improving mental health and as tools for understanding the mind. Several authors suggest neurophysiological and phenomenological parallels and overlaps between psychedelic and meditative states and suggest synergistic effects of both methods. Both psychedelic-assisted therapy and meditation training in the form of mindfulness-based interventions have been experimentally validated with moderate to large effects as alternative treatments for a variety of mental health problems, including depression, addictions, and anxiety disorders. Both demonstrated significant post-acute and long-term decreases in clinical symptoms and enhancements in well-being in healthy participants, in addition. Postulated shared salutogenic mechanisms, include, among others the ability to alter self-consciousness, present-moment awareness and antidepressant action via corresponding neuromodulatory effects. These shared mechanisms between mindfulness training and psychedelic intervention have led to scientists theorizing, and recently demonstrating, positive synergistic effects when both are used in combination. Research findings suggest that these two approaches can complement each other, enhancing the positive effects of both interventions. However, more theoretical accounts and methodologically sound research are needed before they can be extended into clinical practice. The current review aims to discuss the theoretical rationale of combining psychedelics with mindfulness training, including the predictive coding framework as well as research findings regarding synergies and commonalities between mindfulness training and psychedelic intervention. In addition, suggestions how to combine the two modalities are provided.

Challenges and considerations for treating PTSD with medicinal cannabis: the Australian clinician's perspective.

INTRODUCTION: Preclinical and experimental research have provided promising evidence that medicinal cannabis may be efficacious in the treatment of posttraumatic stress disorder (PTSD). However, implementation of medicinal cannabis into routine clinical therapies may not be straightforward. AREAS COVERED: In this review, we describe some of the clinical, practical, and safety challenges that must be addressed for cannabis-based treatment of PTSD to be feasible in a real-world setting. These issues are especially prevalent if medicinal cannabis is to be combined with trauma-focused psychotherapy. EXPERT OPINION: Future consideration of the clinical and practical considerations of cannabis use in PTSD therapy will be essential to both the efficacy and safety of the treatment protocols that are being developed. These issues include dose timing and titration, potential for addiction, product formulation, windows of intervention, and route of administration. In particular, exposure therapy for PTSD involves recall of intense emotions, and the interaction between cannabis use and reliving of trauma memories must be explored in terms of patient safety and impact on therapeutic outcomes.

Indigenous Voices in Psychedelic Therapy: Experiential Learnings from a Community-Based Group Psychedelic Therapy Program.

Novel and traditional psychedelic medicines are attracting interest as potential treatments of mental illness. Before psychedelic therapies can be made available in culturally safe and effective ways to diverse peoples, the field must grapple with the complex legacies of colonialism and ongoing clashes between biomedical and Indigenous Ways of Knowing. This article presents results of a pilot program offering group-based therapy augmented by three sessions of ketamine at a psychedelic dose, for a group of Indigenous participants. This unique project was undertaken in partnership between Roots to Thrive and the Snuneymuxw First Nation to assess this approach's effectiveness and safety for Indigenous peoples. Thematic analysis of qualitative interviews and anonymous feedback received throughout the program from eight participants and two Elders provided rich information on participant motivations, perceived barriers, appreciated and beneficial aspects of the program, and the psychedelic experiences, as well as important directions for further improvement. In addition to challenges, participants attributed significant benefits to the program while highlighting the importance of the involvement of Indigenous team members, the incorporation of traditional approaches to healing, and the cultivation of open and authentic relationships between group participants and facilitators. We discuss important lessons learned and the essential work of reconciliation in, and beyond, psychedelic therapies.

Have Effective Antidepressants Finally Arrived? Developments in Major Depressive Disorder Therapy.

Among the greatest unmet needs in major depressive disorder (MDD) is a lack of effective pharmacotherapies for patients who do not respond to first- and second-line antidepressant medications. After decades of muted progress, optimism regarding the future of MDD therapy rose after scientists serendipitously uncovered the antidepressant effects of ketamine. The discovery of ketamine's antidepressant effects inspired the search for related newer medications, such as S-ketamine. Orally administered NMDA antagonists have also demonstrated considerable promise in recently concluded, late-stage clinical trials. Researchers evaluating an extended-release combination of bupropion (105 mg) and dextromethorphan (45 mg) found that recipients experienced a decline in MADRS total score. Neurosteroids, such as brexanolone and zuranolone, appear to represent another class of antidepressants. These drugs appear to modulate GABA neurotransmission, which has long been known to be a pathway for drugs that are used to treat insomnia and anxiety. After nearly 50 years of legal injunctions against their use, psychedelic drugs have attracted interest among researchers seeking alternative antidepressants. Psilocybin, derived from mushrooms, remains under investigation for its benefits in treatment-resistant depression.

Natural psychedelics in the treatment of depression; a review focusing on neurotransmitters.

Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action of natural psychedelics in the treatment of depression will be discussed. In this review, our focus will be on N, N-dimethyltryptamine (DMT), reversible type A monoamine oxidase inhibitors, mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, ibogaine, muscimol extracted from Amanita spp. mushrooms and ibotenic acid.

Commentary: Access to Psychedelics for Psychological Suffering at the End of Life - Prioritizing Our Priorities.

We agree with Kratina et al. (2023) that the problem of psychological suffering at the end of life deserves attention from a policy standpoint and that psychedelic therapies show promise in this clinical context. However, we argue the following in this rejoinder: (1) disproportionate attention to psychedelics may overstate the current evidence base, potentially diverting resources away from existing evidence-based programs; (2) a more pressing policy priority related to this public health problem is to address population-level inequities in accessing high-quality, early and holistic palliative care, including psychosocial care; and (3) discussions about expanded access to psychedelics must also foreground equity issues.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Letter to the editor on "Increased low-frequency brain responses to music after psilocybin therapy for depression".

The recent publication in the Journal of Affective Disorders titled "Increased low-frequency brain responses to music after psilocybin therapy for depression" identified significant region-of-interest based effects of treatment in the task scans. In this letter to the editor, I am hoping to raise methodological concerns with regards to the ANOVA ROI analysis that were otherwise not acknowledged in this study. These concerns raise questions as to the impact of confounds, including as age and biological sex, on the reported proportion variance explained by the effects of psilocybin treatment for depression.

Increased low-frequency brain responses to music after psilocybin therapy for depression.

BACKGROUND: Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT. METHODS: Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions. RESULTS: Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. LIMITATIONS: Open-label trial. Relatively small sample size. CONCLUSIONS: These data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.

Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020.

BACKGROUND: Growing numbers of people are using psychedelics for personal psychotherapy outside clinical settings, but research on such use is scarce. AIMS: This study investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic 'self-treatment' of mental health conditions or specific worries/concerns in life. METHODS: We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide (N = 1996) or psilocybin mushrooms (N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours. RESULTS: Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes. CONCLUSIONS: This study brings important insights into self-treatment practices with psychedelics in a large international sample. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables.

IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy.

Ibogaine is a powerful psychoactive substance that not only alters perception, mood and affect, but also stops addictive behaviors. Ibogaine has a very long history of ethnobotanical use in low doses to combat fatigue, hunger and thirst and, in high doses as a sacrament in African ritual contexts. In the 1960's, American and European self-help groups provided public testimonials that a single dose of ibogaine alleviated drug craving, opioid withdrawal symptoms, and prevented relapse for weeks, months and sometimes years. Ibogaine is rapidly demethylated by first-pass metabolism to a long-acting metabolite noribogaine. Ibogaine and its metabolite interact with two or more CNS targets simultaneously and both drugs have demonstrated predictive validity in animal models of addiction. Online forums endorse the benefits of ibogaine as an "addiction interrupter" and present-day estimates suggest that more than ten thousand people have sought treatment in countries where the drug is unregulated. Open label pilot studies of ibogaine-assisted drug detoxification have shown positive benefit in treating addiction. Ibogaine, granted regulatory approval for human testing in a Phase 1/2a clinical trial, joins the current landscape of psychedelic medicines in clinical development.

The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology.

The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy.

An Integrative Review of Measures of Spirituality in Experimental Studies of Psilocybin in Serious Illness Populations.

Background: Psilocybin-assisted therapies (PAT) are reemerging as a treatment for complex distress often prompting mystical experiences, enhanced meaning, and spiritual wellbeing. We sought to investigate how measures of spirituality are employed in experimental studies of PAT conducted with seriously ill adults. Methods: We included experimental studies of psilocybin conducted with seriously ill adults, which employed measures that contained spirituality and mysticism concepts within their domains or subdomains. Included studies were peer-reviewed and published in English language (up to December 2021). Results: Seven articles met our inclusion criteria. A total of 12 unique instruments were identified. The most frequently used instruments were the Mystical Experience Questionnaire (MEQ30), the Functional Assessment of Chronic Illness Therapy-Spirituality (FACIT-Sp-12), and the Demoralization Scale (DS-I/II) (used in four studies each), followed by the Persisting Effects Questionnaire (PEQ) (used in three studies). Overall, studies did not consistently define and contextualize spirituality domains and subdomains studied. Conclusions: Despite well-recognized significance of spirituality in PAT, there was considerable heterogeneity in number and types of spirituality measures employed across studies. There also seemed a lack of attention to defining and operationalizing spirituality and its domains and subdomains. This is notable as spirituality and overlapping concepts (eg mystical experiences) contributes substantially to this body of research and patients' therapeutic outcomes. Towards developing more rigorous science of spirituality in PAT research, there is a critical need to evaluate and refine measures of spirituality to enhance their utility and replicability, limit participant burden, and better contextualize spirituality-related findings and outcomes.

Psychotherapists' openness to engage their patients in Psilocybin-Assisted Therapy for mental health treatment.

Despite psychedelic research initially ceasing in the 1970-80s, the findings documented encouraged researchers to re-examine the safety and efficacy of treating mental health with psychedelics. Of particular focus, psilocybin has shown to have therapeutic potential for a variety of mental health problems and was granted breakthrough therapy status by the FDA. Should psilocybin eventually become legally licensed, the success of Psilocybin-Assisted Therapy (PAT) may largely rely on clinicians' openness to engage their eligible patients with PAT. We therefore assessed 119 psychologists' openness to recommend PAT, perceived barriers/facilitators to informing patients about PAT, and factors affecting their openness to involve patients with PAT if FDA approved. While 77.4 % of psychologists agreed they would inform eligible patients about PAT, 91.6 % stated they would still recommend psychotherapies that do not involve psilocybin first. 76.5 % endorsed that knowledge on psilocybin would increase their likelihood to inform patients about PAT. More positive attitudes and beliefs about psilocybin, greater self-reported knowledge of psilocybin, personal history of psychedelic usage, and more positive attitudes towards medical cannabis (MC) was associated with greater openness to engage patients with PAT. Our regression analysis revealed that attitudes towards MC and beliefs about psilocybin were the only significant predictors of psychotherapists' openness towards PAT. These findings provide relevant information to institutions planning educational programs for mental health professionals about psilocybin and Psychedelic-Assisted Therapies.