Aktuality v tématu návykové chování
Think tank racionální politiky závislostí v březnu 2023 připravil dokument s nadpisem "Prohibice nefunguje" (2022)
V podtitulu o dokumentu think tank hovoří jako o "pozičním evidence-based dokumentu k dekriminalizaci a chytré regulaci drogových politik. Celý dokument si můžete pročíst zde: Prohibice nefunguje (2023)
Biologic Commonalities between Mental Illness and Addiction (2013)
Abstract
Epidemiologic studies indicate that co-occurring substance use disorders and psychiatric disorders are frequently found in clinical practice. From a neurobiologic perspective, what do these two seemingly different groups of disorders have in common? Currently, several hypotheses are postulated to explain the high rates of comorbidity. Chronic alcohol and drug use may lead to neuroadaptation in the biologic systems mediating psychiatric disorders. Conversely, co-occurring psychiatric and substance use disorders (SUDs) may represent phenotypic expressions of common premorbid neurobiologic abnormalities. Similar alterations in the dopamine-mediated reward system and various neurotransmitter systems including glutamate, γ-aminobutyric acid, and serotonin are found in both SUDs and numerous psychiatric disorders. Stress and chronic distress with the resultant activation of the hypothalamic-pituitary-adrenal axis and stress system has also been implicated in the pathophysiology of both psychiatric disorders and SUDs. Better understanding the commonalities between the two groups of disorders should lead to more efficacious treatments and targeted prevention strategies.
Epidemiologic survey studies (the National Comorbidity Survey, the Epidemiologic Catchment Area study, and the National Epidemiological Survey on Alcohol and Related Conditions [NESARC]) have emphasized the prevalence of comorbid psychiatric and substance use disorders (SUDs) in community samples of adults. The most recent and largest (N>43,000) comorbidity study to date, NESARC, found strong associations between alcohol dependence and other SUDs and mood, anxiety, and personality disorders.1 As demonstrated in Figure 1,2 statistically significant positive associations were found between almost all drug use disorders and mood and anxiety disorders.3
OVERLAPPING CONDITIONS: SHARED VULNERABILITY2
Because mood disorders increase vulnerability to drug abuse and addiction, the diagnosis and treatment of the mood disorder can reduce the risk of subsequent drug abuse. Because the inverse may also be true, the diagnosis and treatment of drug use disorders may reduce the risk of developing other mental illnesses, and if they do occur, lessen their severity or make them more amenable to effective treatment. Finally, >40% of the cigarettes smoked in the United States are smoked by individuals with a psychiatric disorder, such as major depressive disorder, alcoholism, posttraumatic stress disorder, schizophrenia, or bipolar disorder. Smoking by patients with mental illness contributes greatly to their increased morbidity and mortality.
Comorbidity: Addiction and Other Mental Illnesses. Research Report Series. US Department of Health and Human Services. National Institute of Health. National Institute on Drug Abuse. December 2008. NIH publication 08-5771. Reprinted with permission from the National Institute on Drug Abuse. Copyright 2008.
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A multi criteria decision analysis (MCDA) for evaluating and appraising government policy responses to non medical heroin use (2021)
Abstract
Background: Globally, non-medical heroin use is generating significant public health and social harms, and drug policy about heroin is a controversial field that encompasses many complex issues. Policy responses to illegal heroin markets have varied from militarized eradication of the opium poppy and harsh punishment of users, to more tolerant harm reduction approaches with decriminalized possession and use.
Methods: This paper reports the outcomes of a multi-criteria decision analysis (MCDA) on four generic regulatory regimes of heroin: prohibition, decriminalisation, state control and free market. Invited experts on drug harms, addiction, criminology and drug policy developed a comprehensive set of 27 policy outcome criteria against which these drug policy regimes were assessed.
Results: State control of heroin was identified as the preferred policy option although other policy regimes scored better on specific outcome criteria. The free market model scored better than decriminalisation, with absolute prohibition scoring worst on every criterium. The ranking of the regimes was robust to variations in the criterion-specific weights.
Conclusion: The implications of these findings for the development of future policy responses to heroin and opioids generally are discussed in detail. Despite increasing overdose deaths and an opioid epidemic in North America, prohibition remains the predominant policy approach to heroin regulation at present. It is hoped that the current paper adds to the discussion of finding a valid regulatory alternative.
Keywords: Decriminalization; Drug policy; Heroin; Legalization; Multi-criteria decision analysis; Prohibition; Regulation; Regulatory regimes.
Copyright © 2021. Published by Elsevier B.V.
Conflict of interest statement
Declarations of Interest SR is employed by Transform Drug Policy Foundation, a UK-registered charity engaged in advocacy and campaigns for drug policy and law reform, specifically including establishing a just and effective system of regulation for currently illegal or unregulated drugs. AKS is Head of Research at Drug Science, an independent, not-for-profit organisation addressing drug policy. DN is Chair of Drug Science. FM is co-Director of The Loop UK and the Loop AU, harm reduction non profit NGOs, and a founding member of Drug Science. SR and LP are members of Drug Science. The remaining authors have nothing to disclose.
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Adolescent cannabis use and adult psychoticism: A longitudinal co-twin control analysis using data from two cohorts (2022)
Observational studies have repeatedly linked cannabis use and increased risk of psychosis. We sought to clarify whether this association reflects a causal effect of cannabis exposure or residual confounding. We analyzed data from two cohorts of twins who completed repeated, prospective measures of cannabis use (N = 1544) and cannabis use disorder symptoms (N = 1458) in adolescence and a dimensional measure of psychosis-proneness (the Personality Inventory for DSM-5 Psychoticism scale) in adulthood. Twins also provided molecular genetic data, which were used to estimate polygenic risk of schizophrenia. Both cumulative adolescent cannabis use and use disorder were associated with higher Psychoticism scores in adulthood. However, we found no evidence of an effect of cannabis on Psychoticism or any of its facets in co-twin control models that compared the greater-cannabis-using twin to the lesser-using co-twin. We also observed no evidence of a differential effect of cannabis on Psychoticism by polygenic risk of schizophrenia. Although cannabis use and disorder are consistently associated with increased risk of psychosis, the present results suggest this association is likely attributable to familial confounds rather than a causal effect of cannabis exposure. Efforts to reduce the prevalence and burden of psychotic illnesses thus may benefit from greater focus on other therapeutic targets. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Cannabis Legalization and Detection of Tetrahydrocannabinol in Injured Drivers (2022)
BACKGROUND
The effect of cannabis legalization in Canada (in October 2018) on the prevalence of injured drivers testing positive for tetrahydrocannabinol (THC) is unclear.
METHODS
We studied drivers treated after a motor vehicle collision in four British Columbia trauma centers, with data from January 2013 through March 2020. We included moderately injured drivers (those whose condition warranted blood tests as part of clinical assessment) for whom excess blood remained after clinical testing was complete. Blood was analyzed at the provincial toxicology center. The primary outcomes were a THC level greater than 0, a THC level of at least 2 ng per milliliter (Canadian legal limit), and a THC level of at least 5 ng per milliliter. The secondary outcomes were a THC level of at least 2.5 ng per milliliter plus a blood alcohol level of at least 0.05%; a blood alcohol level greater than 0; and a blood alcohol level of at least 0.08%. We calculated the prevalence of all outcomes before and after legalization. We obtained adjusted prevalence ratios using log-binomial regression to model the association between substance prevalence and legalization after adjustment for relevant covariates.
RESULTS
During the study period, 4339 drivers (3550 before legalization and 789 after legalization) met the inclusion criteria. Before legalization, a THC level greater than 0 was detected in 9.2% of drivers, a THC level of at least 2 ng per milliliter in 3.8%, and a THC level of at least 5 ng per milliliter in 1.1%. After legalization, the values were 17.9%, 8.6%, and 3.5%, respectively. After legalization, there was an increased prevalence of drivers with a THC level greater than 0 (adjusted prevalence ratio, 1.33; 95% confidence interval [CI], 1.05 to 1.68), a THC level of at least 2 ng per milliliter (adjusted prevalence ratio, 2.29; 95% CI, 1.52 to 3.45), and a THC level of at least 5 ng per milliliter (adjusted prevalence ratio, 2.05; 95% CI, 1.00 to 4.18). The largest increases in a THC level of at least 2 ng per milliliter were among drivers 50 years of age or older (adjusted prevalence ratio, 5.18; 95% CI, 2.49 to 10.78) and among male drivers (adjusted prevalence ratio, 2.44; 95% CI, 1.60 to 3.74). There were no significant changes in the prevalence of drivers testing positive for alcohol.
CONCLUSIONS
After cannabis legalization, the prevalence of moderately injured drivers with a THC level of at least 2 ng per milliliter in participating British Columbia trauma centers more than doubled. The increase was largest among older drivers and male drivers. (Funded by the Canadian Institutes of Health Research.)
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he effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation (2022)
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally occurring psychoactive alkaloid, first isolated from Psilocybe mushrooms (Passie et al., 2002). Alongside other tryptamines, including dimethyltryptamine (DMT) and ergolines such as lysergic acid diethylamide (LSD), psilocybin is a partial agonist of serotonin (5-hydroxytryptamine; 5-HT) receptors (Halberstadt and Geyer, 2011) and belongs to a class of drugs called ‘psychedelics’ (Carhart-Harris et al., 2016).
Psilocybe mushrooms, and other psychedelic plants such as peyote and ayahuasca, have been used by Central and South American native groups in sacred spiritual and healing ceremonies for thousands of years (Clarke, 2007). In the West, psilocybin has been used in psychiatric research and in psychodynamic-orientated psychotherapy from the early to mid-1960s, after it was first isolated and later synthesised by Albert Hofmann in 1957 and 1958, respectively (Hofmann et al., 1958, 1959). This research on the effects of psilocybin largely halted when it became a Schedule 1 substance due to international legal controls (Rucker et al., 2020), before a resurgence in the mid-1990s (Passie, 2005; Passie et al., 2002).
Psilocybin produces a non-ordinary state of consciousness characterised by changes in emotional state and perception, including experiences of self, space and time (Hasler et al., 2004; Kraehenmann et al., 2015; Vollenweider et al., 1998, 2007). Previous reports suggest that the psychoactive effects of psilocybin are mainly attributable to partial agonism of the 5HT2A receptor subtype (Halberstadt and Geyer, 2011; Madsen et al., 2019; Passie et al., 2002; Vollenweider et al., 1998).
Pilot studies have reported on the efficacy of psilocybin in, for example, treatment-resistant depression (Carhart-Harris et al., 2016, 2018), major depressive disorder (Davis et al., 2021), terminal-cancer–related anxiety (Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016), obsessive-compulsive disorder (OCD) (Moreno et al., 2006) and alcohol and nicotine dependence (Bogenschutz et al., 2015; Johnson et al., 2014). All reported encouraging efficacy findings, with minimal adverse events (AEs), although these results should be interpreted with caution given that some studies were not specifically designed to robustly test psilocybin’s efficacy (e.g. some had open-label designs or lacked a placebo control arm) and all were limited by small sample sizes. Results from a systematic review of studies conducted prior to psilocybin prohibition in the 1970s were also encouraging (Rucker et al., 2016).
Neural correlates of cognitive and emotional processing are considered important therapeutic targets in the development of novel treatments for treatment-resistant depression and other mental disorders. Recent studies demonstrated that psilocybin and similar psychedelics modulate neural circuits implicated in affective disorders, with potential to reduce clinical symptoms of depression (Carhart-Harris et al., 2012, 2016, 2018).
Social cognitive functioning is an influential factor in the development, progression and treatment of many mental health problems. Deficits in social cognition represent key characteristics of many psychiatric and neurological disorders (Cotter et al., 2018) and may compromise real-world functioning across various settings, including work and independent living (Arioli et al., 2018; Jones et al., 2015). Current interventions for psychiatric disorders include psychosocial techniques, such as psychotherapies and occupational therapy and/or social environment and role interventions, as well as pharmacological treatments. Although these interventions are successful for some, they fail others and are only partially successful in many. Lack of an adequate breadth of interventions for mental health problems, combined with an increasingly overt impact, highlights an urgent need for alternative approaches (NHS Digital, 2014). Given this unmet need for improved treatment of social and emotional functioning deficits, a better understanding of the short- and long-term effects of psilocybin on emotional processing and social cognition is required.
The serotonin system has been reported to represent a promising target for pharmacological modulation of social and emotional functioning and has been implicated in the pathophysiology of various mental health problems (Ciranna, 2006; Švob Štrac et al., 2016). Increasing serotonin levels in healthy participants by administering a selective serotonin reuptake inhibitor promoted prosocial behaviour in one study (Crockett et al., 2010) and reduced processing of negative emotional stimuli in another (Harmer et al., 2004); however, since serotonin reuptake inhibitors block 5-HT uptake, such studies do not provide information on specific 5-HT-receptor functioning in social and emotional functioning. Since psilocybin is a preferential partial agonist of the 5-HT2A and 5-HT1A receptors, it is well-suited for investigation of the relative contributions of these subtypes to aspects of emotional processing. In healthy participants, 5-HT2A/1A-receptor stimulation following psilocybin administration acutely enhanced mood and empathy (Mason et al., 2019; Pokorny et al., 2017), prosocial behaviour (Gabay et al., 2018) and attenuated processing of negative facial expressions and social pain (Bernasconi et al., 2014; Kometer et al., 2012; Preller et al., 2016). While these acute effects of psilocybin indicate that serotonin receptor stimulation is a promising target for improvement of emotional processing, investigation of the longer-term effects is of clinical relevance, as it is unclear whether psilocybin’s prosocial effects persist post-acutely. Furthermore, it has not yet been investigated whether the beneficial effects of psilocybin may also benefit general cognitive abilities. Given the potential for psilocybin as a treatment for a range of conditions, studying its effects on cognition is important.
This study aimed to evaluate the safety and feasibility of simultaneous administration of single doses of either 10 or 25 mg doses of psilocybin compared with placebo in healthy participants, administered in a supervised setting with one-to-one psychological support, and to assess the short- and long-term effects of psilocybin on key domains of cognitive functioning. To our knowledge, this represents the largest randomised controlled trial of psilocybin to date. It is important to study the safety and feasibility of this model of simultaneous administration as it could be a more effective, time- and cost-efficient model of treatment delivery, meaning more patients could potentially benefit from this treatment, if approved. While the psychological support in psilocybin therapy delivered before and after psilocybin administration has been administered in group settings in another recent study by Anderson et al. (2020), the actual administration of psilocybin has only been given on an individual basis in modern studies, to date. Prior to the implementation of legal constraints surrounding psychedelics and subsequent assignment of psilocybin and LSD as Schedule 1 substances, several studies did administer psychedelics and/or psychedelic therapy sessions in a group setting (e.g. Harman et al., 1966; Leary et al., 1963; Pahnke, 1963). This study is the first study since the revival of psychedelic research, to our knowledge, to administer psilocybin to participants simultaneously.
The Increase in Addiction during COVID-19 (2021)
The increase in addiction during COVID-19 is a condition that emerged as an aftermath of COVID-19-related events, for instance, fear of the spread of COVID-19, self-abstention from many activities, and restrictions established by the lockdown measures. This condition includes substance addictions such as drugs and alcohol but also behavioral addictions such as gambling, gaming, pornography, and smartphone and internet misuse.
Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process (2018)
Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by “repression” and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such “anti-amnesic” process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction.
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Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression (2020)
The sigma opioid receptor was proposed as a novel fourth opioid receptor in 1976 to account for the behavioural effects of N-allylnormetazocine (SKF-10,047) which could not be accounted for by the μ (morphine) receptor or κ (ketocyclazocine) receptor1. Rather than causing analgesia, as with morphine, benzomorphans such as SKF-10,047 and pentazocine cause psychotomimesis. Martin proposed that SKF-10,047 was acting as a sigma opioid receptor agonist, in order to cause the psychological and behavioural effects which were observed1. It is now recognized that there are two sigma receptors: The sigma-1 receptor consists of a 223 amino acid long protein, which shares no homology with any other known mammalian protein2. X-ray crystallography analysis of the sigma-1 receptor has revealed a trimeric structure, with each receptor in the trimer having a single transmembrane domain anchoring it to the cytosolic side of the endoplasmic reticulum3. N,N-dimethyltryptamine may be the endogenous sigma-1 receptor ligand despite having low affinity for the sigma-1 receptor4. TMEM97 has now been proposed to be the unrelated “sigma-2 binding site”5.
The sigma-1 receptor has been linked with many diverse disease states and conditions. Sigma-1 receptor agonists appear to remedy symptoms of many mental conditions including depression, Alzheimer’s and drug addiction. Conversely, antagonists at the sigma-1 receptor can be used in the diagnosis and treatment of many cancers; in addition they also have analgesic properties6.
The efficacy of sigma-1 agonists in the treatment of depression has been recognized retrospectively, as many widely used antidepressants have now been shown to also act at the sigma-1 receptor7. Fluoxetine has been found to bind the sigma-1 receptor with reasonable affinity (214 nM)8, although affinity for the 5-HT reuptake transporter was much higher (0.81 nM)8.
Whilst the sigma-1 receptor has been mostly studied for its functions within the nervous system, it is also found to be very highly expressed in a wide range of human tumours that originate from both neuronal and non-neuronal tissues9. This has facilitated the clinical study of cancer through the application of sigma ligands in tumour imaging10, and the identification that sigma-1 receptor antagonists are able to prevent tumour growth, through calcium signalling, phospholipase C (PLC) activation, ER stress, and caspase activation11,12.
Development of new agents is costly and time-consuming. Leading chemists claim that each new chemical entity in drug discovery requires multiple synthetic steps (seven or more) for their production13. There have been a number of previous studies looking for a structural relationship between sigma-1 receptor ligands and their affinity for the sigma-1 receptor14,15. The importance of the nitrogen atom has been shown for the phenylalkylpiperidines and phenylalkylpiperazines14,16. However, evidence exists that more simple molecules can show high affinity for the sigma-1 receptor17,18.
We now determine that simple ammonium salts show clear structure-activity relationships for the sigma-1 receptor. Our simple ammonium salts differ from commonly used sigma-1 receptor ligands, which often contain more than one nitrogen and have complex aromatic ring structures; the simple ammonium salts contain only one nitrogen, and have simple carbon chains. These compounds were found to have high affinity for the unrelated sigma-2 receptor, TMEM975. All but one of the straight-chained ammonium salts described show agonist-like profiles during in vitro studies. One of these, dipentylammonium, is shown to have antidepressant activity in vivo despite showing little activity towards transporters of 5-hydroxytryptamine (serotonin), dopamine or noradrenaline. Furthermore, the branched-chain ammonium salts showed antagonist-like properties during in vitro studies and the two tested were able to prevent tumour growth in vivo.
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New Study Shows Ayahuasca’s Benefits When Used in a Traditional Setting (2020)
Anecdotal accounts about the health benefits of ayahuasca are many, but scientific research has been sparse. A group of independent researchers in the UK have taken a step towards addressing this disparity. In a recently published study, the team of Simon Ruffell, Nige Netzband, and WaiFung Tsang evaluated the effect of ayahuasca on personality traits when the tea is used in a traditional Amazonian framework, as commonly adapted for ayahuasca tourists.
The study found that all participants experienced a significant decrease in neuroticism, as well as considerable increases in agreeableness, after the ayahuasca ceremonies.
Until now, the majority of studies investigating ayahuasca’s effect on personality have taken place in clinical psychotherapeutic frameworks and church-based settings. However, this self-funded study is the first to examine the effects of ayahuasca on personality within Shipibo-style ceremonies that closely resemble the traditional use of the plants within the Peruvian Amazon.
The dataset was collected at the Ayahuasca Foundation retreat and research center located outside of Iquitos, Peru. A total of 24 participants included in the study took place in a twelve-day retreat that included six ayahuasca ceremonies. The study design also included a control group of 24 individuals who were on holiday in Peru who had never used ayahuasca.
To quantitatively measure changes in personality traits, researchers used the NEO Personality Inventory-3, otherwise known as the NEO-PI3, that indexes personality into five primary personality domains including openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism.
Prior to their first ayahuasca ceremony, participants were given a baseline personality measurement using the NEO-PI3, and after the end of their retreat, having completed six ceremonies, participants were once again asked to complete the questionnaire. To measure the long-term effects of ayahuasca on personality change, the questionnaire was sent to participants as a six-month follow-up. Beyond this, researchers also used the Mystical Experience Questionnaire to measure levels of perceived mystical experience post-ceremony.
The reductions in neuroticism were more pronounced than researchers had anticipated.Dr. Simon Ruffell, shared co-first author of the paper, a psychiatrist at Maudsley Hospital, and Senior Research Associate at King’s College, London, identified the fact that neuroticism significantly decreased not just in the short-term, but also in the long-term, six-month follow-up without further use of ayahuasca as one of the most significant findings of this study.
“This is consistent with the growing body of research that suggests psychedelics, and in this case ayahuasca, have major therapeutic potential,” says Ruffell. “High levels of neuroticism are associated with a range of psychiatric conditions, including anxiety, depression, and obsessive-compulsive disorder. Research shows that ayahuasca is able to decrease neuroticism, making it a valuable therapeutic tool for treating such conditions.”
Further, participants who ranked higher on the Mystical Experience Questionnaire, reporting a greater perceived intensity of mystical experience also experienced increased reductions in neuroticism. This finding is in line with previous research that suggests mystical experiences contribute to the therapeutic effect of psychedelics.
Although these results showed multiple similarities with existing findings, there was one major difference between the findings of this study and other studies done in a medical context with psilocybin. Previous research conducted at Johns Hopkins University demonstrated that mystical experiences induced by psilocybin cause increases in openness as opposed to decreases in neuroticism. Although it is true that decreases in neuroticism have been found in psilocybin research, it was not as statistically significant as the increase in trait openness.
“One possible reason that we didn’t find substantial increases in openness might be connected to self-selection bias and that participants were most likely already at a ‘ceiling level’ of openness,” says Ruffell. “In essence, the kind of people who seek out experiences like going to the Amazon to drink ayahuasca are probably already very open, with the participants in our sample having reported higher levels of openness by comparison to the general population.”
Out of the twenty-four participants included in the study, twenty-one were of white American, Canadian, British or European ethnicity, with the remaining three being Asian or Latin. Ruffell attributes the lack of racial diversity among participants to the fact that the study was observational in nature and that the sample was self-selected.
“Because the study was observational, we had no control over those who attended. The majority of the participants were white which is likely a reflection of the kind of person who is naturally able to attend ayahuasca retreats in the Amazon.”
“This might be due to interest,” Ruffell said. “However, it is likely that the lack of racial diversity is also representative of environmental barriers that prevent people from coming to retreats, including factors such as money and the ability to take time off work.”
It remains unclear as to how far the decreases in neuroticism found in this study can be attributed to the visionary states induced by ayahuasca, or the extent to which they were determined by set and setting. Future directions for this research would entail replicating the study in different settings such as clinical, church-based, and neo-shamanic settings.
“Based on our research looking at a limited number of personality measures, it seems that ayahuasca in a ceremonial setting has a similar impact to ayahuasca in other settings,” says Ruffell. “However, as we continue research I imagine that we will likely find that ayahuasca in different settings with slightly different brews is better for different mental health conditions.”
Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study (2021)
Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis. Overall, a statistically significant decrease in BDI-II (13.9 vs. 6.1, p < 0.001), STAI (44.4 vs. 34.3 p < 0.001) scores, and CORE-OM scores were observed (37.3 vs. 22.3 p < 0.001) at post-retreat, as well as a concurrent increase in SCS (3.1 vs. 3.6, p < 0.001). Psychometric improvements were sustained, and on some measures values further decreased at 6-month follow-up, suggesting a potential for lasting therapeutic effects. Changes in memory valence were linked to the observed psychometric improvements. Epigenetic findings were equivocal, but indicated that further research in candidate genes, such as sigma non-opioid intracellular receptor 1 (SIGMAR1), is warranted. This data adds to the literature supporting ayahuasca's possible positive impact on mental health when conducted in a ceremonial context. Further investigation into clinical samples, as well as greater analyses into the mechanistic action of ayahuasca is advised...
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Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo (2021)
Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and timescale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine size and density, driven by an elevated spine formation rate. The structural remodeling occurred quickly within 24 h and was persistent 1 month later. Psilocybin also ameliorated stress-related behavioral deficit and elevated excitatory neurotransmission. Overall, the results demonstrate that psilocybin-evoked synaptic rewiring in the cortex is fast and enduring, potentially providing a structural trace for long-term integration of experiences and lasting beneficial actions.
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Does psychedelic therapy have a transdiagnostic action and prophylactic potential? (2021)
Addressing global mental health is a major twenty-first century challenge. Current treatments have recognised limitations; in this context, new ones that are prophylactic and effective across diagnostic boundaries would represent a major advance. The view that there exists a core of transdiagnostic overlap between psychiatric disorders has re-emerged in recent years, and evidence that psychedelic therapy holds promise for a range of psychiatric disorders supports the position that it may be transdiagnostically effective. Here we propose that psychedelic therapy’s core, transdiagnostically relevant action, lies in its ability to increase neuronal and mental plasticity, thus enhancing the potential for change, which we consider to be a key to its therapeutic benefits. Moreover, we suggest that enhanced plasticity via psychedelics, combined with a psychotherapeutic approach, can aid healthy adaptability and resilience, protective factors for long-term well-being. We present candidate neurological , and psychological markers of this plasticity and link them with a predictive processing model of the action of psychedelics. We propose that a model of psychedelic induced plasticity combined with an adequate therapeutic context has prophylactic and transdiagnostic potential, implying that it could have a broad, positive impact on public health.
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Relational Processes in Ayahuasca Groups of Palestinians and Israelis (19. 5. 2021)
Psychedelics are used in many group contexts. However, most phenomenological research on psychedelics is focused on personal experiences. This paper presents a phenomenological investigation centered on intersubjective and intercultural relational processes, exploring how an intercultural context affects both the group and individual process. Through 31 in-depth interviews, ceremonies in which Palestinians and Israelis drink ayahuasca together have been investigated. The overarching question guiding this inquiry was how psychedelics might contribute to processes of peacebuilding, and in particular how an intercultural context, embedded in a protracted conflict, would affect the group’s psychedelic process in a relational sense. Analysis of the interviews was based on grounded theory. Three relational themes about multilocal participatory events which occurred during ayahuasca rituals have emerged from the interviews: 1) Unity-Based Connection – collective events in which a feeling of unity and ‘oneness’ is experienced, whereby participants related to each other based upon a sense of shared humanity, and other social identities seemed to dissolve (such as national and religious identities). 2) Recognition and Difference-Based Connection – events where a strong connection was made to the other culture. These events occurred through the expression of the other culture or religion through music or prayers, which resulted in feelings of awe and reverence 3) Conflict-related revelations – events where participants revisited personal or historical traumatic elements related to the conflict, usually through visions. These events were triggered by the presence of ‘the Other,’ and there was a political undertone in those personal visions. This inquiry has revealed that psychedelic ceremonies have the potential to contribute to peacebuilding. This can happen not just by ‘dissolution of identities,’ but also by providing a space in which shared spiritual experiences can emerge from intercultural and interfaith exchanges. Furthermore, in many cases, personal revelations were related to the larger political reality and the history of the conflict. Such processes can elucidate the relationship between personal psychological mental states and the larger sociopolitical context...
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study (10. 5. 2021)
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation...
Spontaneous and deliberate creative cognition during and after psilocybin exposure (8. 4. 2021)
Abstract
Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking. Acutely, psilocybin increased ratings of (spontaneous) creative insights, while decreasing (deliberate) task-based creativity. Seven days after psilocybin, number of novel ideas increased. Furthermore, we utilized an ultrahigh field multimodal brain imaging approach, and found that acute and persisting effects were predicted by within- and between-network connectivity of the default mode network. Findings add some support to historical claims that psychedelics can influence aspects of the creative process, potentially indicating them as a tool to investigate creativity and subsequent underlying neural mechanisms. Trial NL6007; psilocybin as a tool for enhanced cognitive flexibility; https://www.trialregister.nl/trial/6007.
Introduction
Creativity is an essential cognitive ability linked to all areas of our everyday life, allowing us to adapt to an ever-changing environment and come up with ways to solve problems. Although arguably difficult to define, the creative process has been viewed as a dynamic process1,2, requiring shifting between different modes of thought in order to reach an end result3. These modes include divergent thinking (DT), which consists of generating novel and original ideas, and convergent thinking (CT), the subsequent evaluation of generated ideas in regards to their usefulness and effectiveness4,5. Importantly, as well as being an essential process for everyday functioning, the (in)ability to think “outside of the box” has also been associated with psychological disorders, such as depression and anxiety6,7. Here, it has been regarded both as a transdiagnostic process, i.e., a risk or maintaining factor shared across disorders, and as a potential therapeutic intervention, promoting adaptive interpretations and coping strategies7,8. Thus taken together, finding a way to enhance creative thinking is of broad interest among multiple disciplines, ranging from industry to psychopathology...
Self-blinding citizen science to explore psychedelic microdosing (2021)
Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.
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Ecologies of drug war and more-than-human health: The case of a chemical at war with a plant (2020)
Drawing on an ecological approach, we trace how the political-economy of drug wars are locally materialised in relation to health. We take the case of coca cultivation and eradication as our example. To make our analysis, we trace the different ways that the chemical glyphosate is materialised in a war with the coca plant in Colombia. Glyphosate has been used for decades in aerial fumigation campaigns to eradicate illicit coca cultivation. Our analysis traces the more-than-human effects of glyphosate in relation to health. This leads us to outline a more-than-human approach to harm reduction; a harm reduction which positions health as a matter of ecology, paying attention not only to the nonhuman actors affecting human health but also to the health of environments which are themselves always in-the-making. We envisage harm reduction as a collaboration in which humans 'become-with' their environments.
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Monitoring and evaluating changes in cannabis policies: insights from the Americas (2020)
This report provides an overview of the changes in cannabis policies in the Americas and the evidence emerging from evaluations of their impact. Highlighting the challenges in monitoring and evaluating regulatory changes in the drugs field, it will be of particular interest to those involved in planning or evaluating any modifications to cannabis regulation.
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Cannabidiol Ameliorates Cognitive Function via Regulation of IL-33 and TREM2 Upregulation in a Murine Model of Alzheimer's Disease (2021)
There is a dire need for due innovative therapeutic modalities to improve outcomes of AD patients. In this study, we tested whether cannabidiol (CBD) improves outcomes in a translational model of familial AD and to investigate if CBD regulates interleukin (IL)-33 and triggering receptor expressed on myeloid cells 2 (TREM2), which are associated with improved cognitive function. CBD was administered to 5xFAD mice, which recapitulate early onset, familial AD. Behavioral tests and immunoassays were used to evaluate cognitive and motor outcomes. Our findings suggest that CBD treatment enhanced IL-33 and TREM2 expression, ameliorated the symptoms of AD, and retarded cognitive decline.
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Public Policy Statement on Advancing Racial Justice in Addiction Medicine (2021)
Addiction involves complex interactions among an individual’s brain circuits, genetics, the environment, and their life experiences.1 Racism disproportionately shapes the environment and life experiences of Black, Hispanic/Latin, Asian, Pacific Islander, Native American, and other racially oppressed and disenfranchised people (hereinafter collectively referred to as Black, Indigenous, People of Color (BIPOC), adversely influencing both their risk of developing addiction and their access to evidence-based addiction treatment services. While police and civilian murders of Black people in the United States of America have highlighted the deadly consequences of racism, they have also illuminated the impact of the long-standing systemic racism in the United States. Systemic racism has been defined as “a system in which public policies, institutional practices, cultural representations, and other norms work in various, often reinforcing ways to perpetuate racial group inequity.”
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A mechanistic model of the neural entropy increase elicited by psychedelic drugs (2020)
Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
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Aerosol Gas-Phase Components from Cannabis E‑Cigarettes and Dabbing: Mechanistic Insight and Quantitative Risk Analysis (2019)
Consumption of cannabis by nontraditional methods has surged sincethe advent of legalization in North America and worldwide. Inhaling cannabis extractsusing vaporizers and via dabbing has risen in popularity, while concerns over productsafety have not hindered their proliferation. The work herein is thefirst step towardassessing the safety of vaporizing and dabbing concentrated cannabis extracts as afunction of gas-phase reaction products. The gas-phase thermal degradants ofΔ9-tetrahydrocannabinol (THC) have not been previously investigated. It was found thatusers may be exposed to concerning degradants such as methacrolein, benzene, andmethyl vinyl ketone when using cartridge vaporizers and dabbing. It was shown thatTHC alone and mixed with terpenes generated similar degradation products and, most notably, elevated levels of isoprene.Importantly, it was shown that added terpenes led to higher levels of gas-phase products compared to THC alone. To estimatecancer and noncancer risks associated with exposure to these and other degradants, quantitative risk assessment was applied toexperimentally determined values for dabbing and vaping and literature-sourced levels of hazardous components in cannabissmoke. Overall, gas-phase aerosol products had significantly lower values in dabbing and vaporizing compared to cannabissmoking, although these results should be interpreted in light of potential variations in degradant levels due to disparate usagepatterns and the dangers of the higher aerosol concentration of THC.
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What Do You Know About Maryjane? A Systematic Review of the Current Data on the THC:CBD Ratio (2020)
Background: Ratios of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact metabolism and therapeutic effects of cannabis. Currently, no states with legalized medical or recreational cannabis consider ratios THC:CBD in regulations. Objective: Determine what THC:CBD ratios are selected for use in clinical cannabis trials and what is the rationale. Methods: This is a systematic literature review of Central, CINAHL, Embase, PsycInfo, and PubMed of the last 10 years of English language medical cannabis publications highlighting THC:CBD ratios. Included were clinical studies of products containing and listing both THC and CBD ratios, percentages, or weighted amounts. Case reports and series, abstracts, reviews, and meta-analysis were excluded. Non-human, non-therapeutic, or studies examining approved cannabis pharmaceuticals were excluded. Results: Four hundred and seventy-nine (479) unique references were found, of which 11 met inclusion criteria. THC:CBD ratios listed and/or calculated: 1:0, 22:1, 2:1, 1:1, 1:2, 1:6, 1:9, 1:20, 1:33, 1:50, and 0:1. Rationale for ratios selected was often not listed, or simply trivialized as the ratios available to patients in the area, or ratios that were pharmaceutically available throughout the study country. One study compared ratios of high and low THC:CBD, but did not specify the ratios. Conclusion: The medical and scientific communities have not drawn substantive conclusions nor thoroughly explored THC:CBD ratios for “best practice” treatment of different disease processes and their sequelae. While there is evidence that cannabis provides medical benefits, research is lacking on standardization of medical cannabis use in modern medical practices.
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