-
Frontiers in Psychiatry 2023Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This... (Review)
Review
BACKGROUND
Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics.
METHODS
A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both and studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A.
RESULTS
Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents.
CONCLUSION
Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.
PubMed: 37435405
DOI: 10.3389/fpsyt.2023.1197890 -
Frontiers in Psychiatry 2023Cannabis use disorder (CUD) is prevalent in ~2-5% of adults in the United States and is anticipated to increase as restrictions to cannabis decrease and...
INTRODUCTION
Cannabis use disorder (CUD) is prevalent in ~2-5% of adults in the United States and is anticipated to increase as restrictions to cannabis decrease and tetrahydrocannabinol (THC) content in cannabis products increase. No FDA-approved medications for CUD are currently available, despite trials of dozens of re-purposed and novel drugs. Psychedelics have garnered interest as a therapeutic class in other substance use disorders, and self-report surveys suggest they may result in positive outcomes for CUD. Herein, we review the existing literature pertaining to psychedelic use in persons with or at risk for CUD and consider the potential rationale underpinning psychedelics as a treatment for CUD.
METHODS
A systematic search was performed in several databases. Inclusion criteria were primary research reporting use of psychedelics or related substances and CUD for treatment in human subjects. Exclusion criteria were results including psychedelics or related substances without changes in cannabis use or risks associated with CUD.
RESULTS
Three hundred and five unique results were returned. One article was identified using the non-classical psychedelic ketamine in CUD; three articles were identified as topically relevant based on their secondary data or consideration of mechanism. Additional articles were reviewed for purposes of background, review of safety considerations, and formulating rationale.
CONCLUSION
Limited data and reporting are available on the use of psychedelics in persons with CUD, and more research is needed given the anticipated increase in CUD incidence and increasing interest in psychedelic use. While psychedelics, broadly, have a high therapeutic index with infrequent serious adverse effects, particular adverse effects at risk in the CUD population, such as psychosis and cardiovascular events, should be considered. Possible mechanisms by which psychedelics have therapeutic potential in CUD are explored.
PubMed: 37435402
DOI: 10.3389/fpsyt.2023.1144276 -
Journal of Psychopharmacology (Oxford,... Jul 2023The classical psychedelics, psilocybin, peyote, ayahuasca/-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric... (Review)
Review
BACKGROUND
The classical psychedelics, psilocybin, peyote, ayahuasca/-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials.
METHODS
We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance.
RESULTS
We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias.
CONCLUSION
Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity.
Topics: Humans; Hallucinogens; Randomized Controlled Trials as Topic; Lysergic Acid Diethylamide; Psilocybin; Anxiety Disorders
PubMed: 37403379
DOI: 10.1177/02698811231180276 -
Innovations in Clinical Neuroscience 2023This systematic review aims to evaluate the impact of psilocybin on patients experiencing psychiatric symptoms, with a focus on health-related quality of life (HRQoL)... (Review)
Review
OBJECTIVE
This systematic review aims to evaluate the impact of psilocybin on patients experiencing psychiatric symptoms, with a focus on health-related quality of life (HRQoL) and safety.
METHOD OF RESEARCH
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed database and identified studies published from January 2011 to December 2021 pertaining to the impact of psilocybin on psychiatric symptoms. Two authors independently conducted a focused analysis and reached a final consensus on five studies meeting the specific selection criteria. Study bias was addressed using the Cochrane risk of bias tool.
RESULTS
The impact of psilocybin on psychiatric symptoms was examined in five randomized controlled trials (RCTs). Four studies administered 1 to 2 doses of psilocybin, with doses ranging from 14mg/70kg to 30mg/70kg, and one study administered a fixed dose of 25mg to all participants. Administration of psilocybin resulted in significant and sustained reduction in symptoms of anxiety and depression, enhanced sense of wellbeing, life satisfaction, and positive mood immediately after psilocybin administration and up to six months after conclusion of treatment. All studies included some form of psychotherapy, and none reported serious adverse effects.
CONCLUSION
RCTs show the efficacy of psilocybin in the treatment of anxiety and depression symptoms, as well as improvement in HRQoL, and no serious side effects. However, additional research is necessary to characterize predictors of treatment response, patient screening requirements, effectiveness in broader clinical populations, and guidelines for psilocybin-assisted psychotherapy.
PubMed: 37387703
DOI: No ID Found -
Therapeutic Advances in... 2023Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the... (Review)
Review
BACKGROUND
Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the 'psychedelic afterglow', have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period.
OBJECTIVES
This systematic review provides an overview of subacute effects of psychedelics.
METHODS
Electronic databases (MEDLINE, Web of Science Core Collection) were searched for studies that assessed the effects of psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) on psychological outcome measures and subacute adverse effects in human adults between 1950 and August 2021, occurring between 1 day and 1 month after drug use.
RESULTS
Forty-eight studies including a total number of 1,774 participants were eligible for review. Taken together, the following subacute effects were observed: reductions in different psychopathological symptoms; increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes; mixed changes in personality/values/attitudes, and creativity/flexibility. Subacute adverse effects comprised a wide range of complaints, including headaches, sleep disturbances, and individual cases of increased psychological distress.
DISCUSSION
Results support narrative reports of a subacute psychedelic 'afterglow' phenomenon comprising potentially beneficial changes in the perception of self, others, and the environment. Subacute adverse events were mild to severe, and no serious adverse events were reported. Many studies, however, lacked a standardized assessment of adverse effects. Future studies are needed to investigate the role of possible moderator variables and to reveal if and how positive effects from the subacute window may consolidate into long-term mental health benefits.
PubMed: 37284524
DOI: 10.1177/20451253231172254 -
The Primary Care Companion For CNS... May 2023To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients....
To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients. MEDLINE(R), Embase, APA PsycINFO, Cochrane, and CINAHL were systematically searched on June 3, 2022, with no date restrictions using the following string: (psilocybin) AND (psychedelics) AND (MRI) OR (fMRI)) OR (PET)) OR (SPECT)) OR (imaging)) OR (neuroimaging)). After duplicates were removed from 946 studies, 391 studies remained, of which 8 qualified for full-text analysis, but only 5 fulfilled the eligibility criteria of randomized, double-blind, or open-label neuroimaging study with psilocybin treatment in depressed patients. The Covidence platform was used for deduplication and bias assessment. The data points included concomitant psychological intervention, modality of neuroimaging technique, changes in depression scores, brain functional changes, and association between functional and psilocybin response. Assessment bias was assessed with the standard risk of bias tool for randomized controlled trials and the tool for risk of bias in nonrandomized studies of interventions. Four studies were open-label, and one was a combined open-label and randomized controlled trial using functional magnetic resonance imaging. Psilocybin-assisted psychotherapy was administered in 3 studies, 1 in refractory and 2 in nonrefractory patients. The remaining 2 studies were in refractory patients. The transient increase in psilocybin-induced global connectivity in major neural tracts and specific areas of brain activation was associated with antidepressant response. Transient functional brain changes with psilocybin therapy resemble the "brain reset" phenomenon and may serve as the putative predictors of psilocybin antidepressant response.
Topics: Humans; Antidepressive Agents; Brain; Depression; Psilocybin; Psychotherapy; Randomized Controlled Trials as Topic
PubMed: 37230065
DOI: 10.4088/PCC.22r03419 -
Behavioral Sciences (Basel, Switzerland) Mar 2023Depression is a common mental health issue that affects 280 million people in the world with a high mortality rate, as well as being a leading cause of disability.... (Review)
Review
Depression is a common mental health issue that affects 280 million people in the world with a high mortality rate, as well as being a leading cause of disability. Psychopharmacological therapies with psychedelics, particularly those with psilocybin, are showing promising potential for the treatment of depression, among other conditions. Some of their benefits include a rapid and exponential improvement in depressive symptoms and an increased sense of well-being that can last for months after the treatment, as well as a greater development of introspective capacity. The aim of this project was to provide experimental evidence about therapeutic procedures along with psilocybin for the treatment of major depressive disorder. The project highlights eight studies that examined this condition. Some of them dealt with treatment-resistant depression while others dealt with depression due to a life-threatening disease such as cancer. These publications affirm the efficiency of the psilocybin therapy for depression, with only one or two doses in conjunction with psychological support during the process.
PubMed: 37102811
DOI: 10.3390/bs13040297 -
BJPsych Open Apr 2023There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. (Review)
Review
BACKGROUND
There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.
AIMS
To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.
METHOD
MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.
RESULTS
The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.
CONCLUSIONS
Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
PubMed: 37066662
DOI: 10.1192/bjo.2023.36 -
Scientific Reports Mar 2023There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and... (Meta-Analysis)
Meta-Analysis
There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and addiction-like behaviors underlying substance use disorders and obesity. Regarding obesity, a systematic review of the literature with a meta-analysis of such data is lacking. Following a systematic review of the literature, we performed random-effects meta-analyses to determine group differences in case-control studies comparing DD2lR between individuals with obesity and non-obese controls and prospective studies of pre- to post-bariatric surgery DD2lR changes. Cohen's d was used to measure effect size. Additionally, we explored factors potentially associated with group differences in DD2lR availability, such as obesity severity, using univariate meta-regression. In a meta-analysis including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, striatal DD2lR availability did not significantly differ between obesity and controls. However, in studies comprising patients with class III obesity or higher, group differences were significant, favoring lower DD2lR availability in the obesity group. This effect of obesity severity was corroborated by meta-regressions showing inverse associations between the body mass index (BMI) of the obesity group and DD2lR availability. Post-bariatric changes in DD2lR availability were not found, although a limited number of studies were included in this meta-analysis. These results support lower DD2lR in higher classes of obesity which is a more targeted population to explore unanswered questions regarding the RDS.
Topics: Humans; Receptors, Dopamine D2; Dopamine; Prospective Studies; Tomography, X-Ray Computed; Obesity; Positron-Emission Tomography; Bariatric Surgery
PubMed: 36973321
DOI: 10.1038/s41598-023-31250-2 -
Toxics Feb 2023Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause... (Review)
Review
Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.
PubMed: 36851023
DOI: 10.3390/toxics11020148