Treating cannabis use disorder remains a significant challenge in the field of addiction medicine. Some recent studies point to psychedelic-assisted psychotherapy as a potential treatment option for substance use disorders. The objective of this study was therefore to explore the impact of naturalistic psychedelic experiences on cannabis use and psychological flexibility. An online retrospective survey was carried out on 152 cannabis users who also reported a significant experience induced by psychedelics in the past. Following a psychedelic experience, there was a significant and sustained reduction of average CUDIT score (p < .001), frequency of cannabis use (p < .001), and acute duration of daily intoxication (p < .001). Cannabis use reduction during the first month post-experience was significantly associated with the intensity of the mystical experience (p = .01). Participants reported a concomitant increased lasting improvement of psychological flexibility following the experience (p < .001), which was correlated to the intensity of the mystical experience during the first month post-experience (p = .04). This study demonstrates that naturalistic psychedelic experiences may be followed by a decrease in cannabis use. Positive health outcomes appear potentially connected to the intensity of the mystical experience, as well as an improvement in psychological flexibility.

BACKGROUND: The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the management of chronic MSK pain remains to be determined. This study examined 1) the rate, patterns of use, and self-reported efficacy of cannabis use among patients with chronic MSK pain and 2) the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.
METHODS: Self-reported cannabis use and perceived efficacy were prospectively collected from chronic MSK pain patients presenting to the Orthopaedic Clinic at the University Health Network, Toronto, Canada. The primary dependent variable was current or past use of cannabis to manage chronic MSK pain; bivariate and multivariable logistic regression were used to identify patient characteristics independently associated with this outcome. Secondary outcomes were summarized descriptively, including self-perceived efficacy among cannabis users, and interest as well as barriers to cannabis use among cannabis non-users.
RESULTS: The sample included 629 patients presenting with chronic MSK pain (mean age: 56±15.7 years; 56% female). Overall, 144 (23%) reported past or present cannabis use to manage their MSK pain, with 63.7% perceiving cannabis as very or somewhat effective and 26.6% considering it as slightly effective. The strongest predictor of cannabis use in this study population was a history of recreational cannabis use (OR 12.7, p<0.001). Among cannabis non-users (N=489), 65% expressed interest in using cannabis to manage their chronic MSK pain, but common barriers to use included lack of knowledge regarding access, use and evidence, and stigma.
CONCLUSIONS: One in five patients presenting to an orthopaedic surgeon with chronic MSK pain are using or have used cannabis with the specific intent to manage their pain, and most report it to be effective. Among non-users, two-thirds reported an interest in using cannabis to manage their MSK pain, but common barriers to use existed. Future double-blind placebo-controlled trials are required to understand if this reported efficacy is accurate, and what role, if any, cannabis may play in the management of chronic MSK pain.

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

BACKGROUND: Since late 2019, fortification of \'regular\' cannabis plant material with synthetic cannabinoid receptor agonists (SCRAs) has become a notable phenomenon on the drug market. As many SCRAs pose a higher health risk than genuine cannabis, recognizing SCRA-adulterated cannabis is important from a harm reduction perspective. However, this is not always an easy task as adulterated cannabis may only be distinguished from genuine cannabis by dedicated, often expensive and time-consuming analytical techniques. In addition, the dynamic nature of the SCRA market renders identification of fortified samples a challenging task. Therefore, we established and applied an in vitro cannabinoid receptor 1 (CB1) activity-based procedure to screen plant material for the presence of SCRAs.
METHODS: The assay principle relies on the functional complementation of a split-nanoluciferase following recruitment of β-arrestin 2 to activated CB1. A straightforward sample preparation, encompassing methanolic extraction and dilution, was optimized for plant matrices, including cannabis, spiked with 5 µg/mg of the SCRA CP55,940.
RESULTS: The bioassay successfully detected all samples of a set (n = 24) of analytically confirmed authentic Spice products, additionally providing relevant information on the \'strength\' of a preparation and whether different samples may have originated from separate batches or possibly the same production batch. Finally, the methodology was applied to assess the occurrence of SCRA adulteration in a large set (n = 252) of herbal materials collected at an international dance festival. This did not reveal any positives, i.e. there were no samples that yielded a relevant CB1 activation.
CONCLUSIONS: In summary, we established SCRA screening of herbal materials as a new application for the activity-based CB1 bioassay. The simplicity of the sample preparation, the rapid results and the universal character of the bioassay render it an effective and future-proof tool for evaluating herbal materials for the presence of SCRAs, which is relevant in the context of harm reduction.

BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD\'s analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD\'s effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC).
METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance).
CONCLUSIONS: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD\'s analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans.
BACKGROUND: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

Cannabis-related tweets were collected between January and April 2022 to estimate the availability and characteristics of cannabis products advertised on Twitter amid the legalization of recreational cannabis in Thailand. The Twitter API was called using the tweepy Python library to collect cannabis-related tweets in the Thai language. A total of 185,558 unique tweets were collected over the duration of the data collection period based on 83 search terms. Twenty thousand random tweets were manually coded by four Thai native speakers to assess the volume and characteristics of tweets proposing cannabis. 72.6% of collected tweets from the 20,000 random samples were coded as relevant to the study. 54.6% of relevant tweets were advertising cannabis products, 29.8% were personal communications, and 15.6% were related to news or media content. Among the tweets that advertised cannabis products, 94.4% proposed cannabis flower, 2.4% cannabis edibles and 1.8% cannabis concentrates. Consumption of potent forms of cannabis such as cannabis edibles and concentrates increase the risk of harmful side-effects, especially in a population with limited knowledge about these products. Our findings call for additional monitoring efforts and for increasing the public awareness on potent cannabis products emerging in Thailand.

After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC-MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)-HHCP, iso-HHCP, cis-HHCP, and abn-HHCP) and two ketones (possible intermediates to (9R)-HHCP and abn-HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)-HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn-HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso-HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.

Canada legalized the use of non-medical cannabis in 2018. This study examines youth and young adults\' knowledge and perceptions of harms, benefits, and education around cannabis use since legalization. An online survey was completed by a convenience sample of 1,759 individuals aged 12-25 years living in Manitoba, Canada. Most participants (n = 1,525, 86.7%) reported receiving education on the potential effects/harms related to cannabis; the most common topics included driving and cannabis use (79.9%), the mental harms of cannabis (67.4%), and addiction and dependency (66.3%). Youth who reported using cannabis more than once (n = 1,203) were more knowledgeable about the effects of cannabis than youth who never used cannabis or used cannabis once (n = 580; mean score: 6.6 versus 5.7 out of 8, respectively; p < .001). Vaping cannabis oil was perceived as the most harmful cannabis product among all participants. Among participants with experience using cannabis, the most frequently reported benefits were relaxation, improved sleep, and enhanced enjoyment of food/music. Half of the participants reported ever being in a car with someone driving high, of which, 40% of these participants reported doing so in the last 30 days. Future tailored education is needed to address knowledge related to cannabis use among youth and young adults who use and do not use cannabis.

The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field\'s understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.

The objective of this research was to evaluate the efficiency of aqueous enzymatic extraction (AEE) to obtain oil from hemp seeds (Cannabis sativa L.) grown in northern Morocco. Optimisation of AEE extraction parameters, including pH, enzyme concentration (hemicellulase, protease and pectinase), temperature and incubation time, to maximize oil yield was achieved using response surface methodology with a central composite design. For comparison, the solvent extraction (Soxhlet) (SE) method was also used. Optimized hydrolysis conditions involved incubation for 4 hours at 60°C with a pH of 6.5, using a multi-enzyme preparation comprising protease, hemicellulase and pectinase at concentrations of 55, 202.5 and 234 U/mg, respectively. Referring to the conventional Soxhlet extraction (SE), Aqueous Enzymatic Extraction (AEE) achieved a 30.65% oil recovery rate under the optimized parameters mentioned above. The use of enzymes produced an oil that was more stable against oxidation than the solvent-extracted oil, with a peroxide value (PV) of 19.54 and 47.87 meq O 2 /kg, respectively. Furthermore, HPLC-DAD analysis of tocopherol content indicated a higher total tocopherol content (547.2 mg/kg) in Aqueous Enzymatic Extraction (AEE) compared to Soxhlet Extraction (SE) (513.51 mg/kg), with γ-tocopherol being the predominant form. No significant differences in fatty acid composition were observed between the two extraction methods with linoleic acid and alpha-linolenic acid being the predominant constituents.