Driving-related behaviors, attitudes, and perceptions among Australian medical cannabis users: results from the CAMS 20 survey

Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surveyed driving-related behaviors, attitudes, and perceptions among Australian medical cannabis (MC) users. Of the 1063 respondents who reported driving a motor vehicle in the past 12 months, 28% (297/1063) reported driving under the influence of cannabis (DUIC). Overall, 49–56% of respondents said they typically drive within 6 h of MC use, depending on the route of administration (oral or inhaled). Non-medical cannabis (NMC) was perceived to be more impairing for driving than MC. Binary logistic regression revealed associations between likelihood of DUIC and (1) inhaled routes of cannabis administration, (2) THC-dominant products, (3) illicit rather than prescribed use, (4) believing NMC does not impair driving, and (5) not being deterred by roadside drug testing. Overall, these findings suggest there is a relatively low perception of driving-related risk among MC users. Targeted education programs may be needed to highlight the potential risks associated with DUIC, and further research is needed to determine whether driving performance is differentially affected by MC and NMC.

Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases. Some of these include central nervous system (CNS) diseases and dysfunctions such as forms of epilepsy, multiple sclerosis, Parkinson’s disease, pain and neuropsychiatric disorders. In addition, the endogenously produced cannabinoid lipids, endocannabinoids, are critical for normal CNS function, and if controlled or modified, may represent an additional therapeutic avenue for CNS diseases. This review discusses in vitro cellular, ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies. In addition, the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases. Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

A Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Effects of CBN With and Without CBD on Sleep Quality

The present study sought to determine the effects of cannabinol (CBN) alone and in combination with cannabidiol (CBD) on sleep quality. This was a double-blind, randomized, placebo-controlled study conducted between May and November 2022. Participants were randomized to receive either (a) placebo, (b) 20 mg CBN, (c) 20 mg CBN + 10 mg CBD, (d) 20 mg CBN + 20 mg CBD, or (e) 20 mg CBN + 100 mg CBD for seven consecutive nights. Participants were 18–55 years of age who self-rated sleep quality as “very poor” or “poor.” The primary endpoint was sleep quality, while secondary endpoints included sleep onset latency, number of awakenings, wake after sleep onset (WASO), overall sleep disturbance, and daytime fatigue

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males

Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products.

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral D8-Tetrahydrocannabivarin in Healthy Participants

Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses. This was a two-phase, dose-ranging, placebo-controlled trial of the D8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n = 3). Phase 2 used a double-blind, random- ized, within-participant crossover design (n = 18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose.

THC-O-Acetate: Scarce Evidence for a Psychedelic Cannabinoid

There is a growing interest in semi-synthetic cannabinoids, including THC-O-acetate (THC-Oac). Some cannabis marketers and users have claimed that THC-Oac produces psychedelic effects; the current study is the first to examine this claim. Researchers developed an online survey for THC-Oac consumers based on previous cannabis and psychedelic use surveys and in consultation with the moderator of an online forum. The survey assessed the experiential profile of THC-Oac and included items from the Mystical Experience Questionnaire (MEQ), an instrument for assessing psychedelic experiences. Participants reported a low to moderate level of cognitive distortions (altered sense of time, difficulties concentrating, difficulties with short-term memory) and few visuals or hallucinations. Participants’ responses were significantly below the threshold for a complete mystical experience on all four MEQ dimensions. Participants who had used classic (5-HT2A agonist) psychedelics had lower scores on all MEQ dimensions. When asked directly, 79% responded that using THC-Oac is “not at all” or “a little” of a psychedelic experience. Some reports of psychedelic experiences may be due to expectations or contaminants. Those having prior experience with classic psychedelics had lower ratings of mystical experiences.

The Use of Cannabinoids in the Treatment of Inflammatory Bowel Disease (IBD): A Review of the Literature

Around the world, about 15 to 40% of individuals with inflammatory bowel disease (IBD) rely on cannabis and cannabinoids to reduce the need for other medications, as well as increase appetite and reduce pain. Whereas more and more patients continue to report benefits accruing from cannabis and cannabinoid usage in IBD, agreement relative to the use of cannabis and its derivatives in IBD remains unclear. This paper reviewed the interplay between cannabinoid use and IBD disease treatment, remission, or symptom relief. The study was conducted from a systematic review perspective. It involved consulting literature from published original research articles, noting outcomes, and performing a meta-analysis to identify trends and draw conclusions. The selected articles were those that had been published in a 10-year period ranging between 2012 and 2022. The motivation was to ensure recency and also relevance to contemporary scientific research and clinical environment practices.

Cannabis and cannabinoid medications for the treatment of chronic orofacial pain: A scoping review

To collate and summarize existing evidence for the use of cannabis and cannabinoids to treat chronic orofacial pain (COP) by oral and maxillofacial surgeons (OMFS), oral medicine specialists (OMS), and orofacial pain specialists (OPS). We systematically screened for sources including a measure of effect of a cannabinoid compound on pain in COP patients that might be treated by our target specialists. Sources were selected by two authors independently. Sources were summarized by country, publication date, objective(s), COP condition(s) studied, cannabinoid(s) studied, methods, results, limitations, and conclusions. A thematic analysis and word cloud were conducted to elucidate commonalities, emphases, and gaps amongst identified sources.

Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment

Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS). This review describes the ECS, its role in the central nervous system, how it is dysregulated in FXS, and the potential role of cannabidiol as a treatment for FXS. FXS is caused by deficiency or absence of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, typically due to the presence of >200 cytosine, guanine, guanine sequence repeats leading to methylation of the FMR1 gene promoter.

Cannabis and Cannabinoid Medications for the Treatment of Chronic Orofacial Pain: A Scoping Review

We systematically screened for sources including a measure of effect of a cannabinoid compound on pain in COP patients that might be treated by our target specialists. Sources were selected by two authors independently. Sources were summarized by country, publication date, objective(s), COP condition(s) studied, cannabinoid(s) studied, methods, results, limitations, and conclusions. A thematic analysis and word cloud were conducted to elucidate commonalities, emphases, and gaps amongst identified sources.

Proapoptotic RECS1: a requisite gateway to lysosomal dysfunction and death

For a long time since their discovery by Christian de Duve in the 1950s, lysosomes have been referred to almost exclusively as passive garbage bags; the endpoint in the degradation of intra- and extracellular cargo. The catabolic function of lysosomes is accomplished by an array of more than 60 acid hydrolases, which together break down a wide variety of biological macromolecules, including proteins, lipids, carbohydrates, and nucleic acids, for reutilization in the metabolic processes of the cell. For their optimal function, these enzymes require an acidic intraluminal pH of ~4.5, which is maintained by the joint action of a proton pump, the vacuolar H+-ATPase, and several ion channels embedded in the lysosomal limiting membrane. Nowadays, lysosomes are envisioned as complex signaling hubs, integrating diverse stimuli about the cell’s metabolic status to coordinate different adaptive responses (Ballabio and Bonifacino, 2020). The lysosome can also induce cell death signals in response to certain conditions, such as infections and treatment with lysosomotropic drugs, which leads to lysosomal membrane permeabilization (LMP) and the release of cathepsins, resulting in lysosomal-mediated cell death.

Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be
used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors