Understanding feeling “high” and its role in medical cannabis patient outcomes

Our study uses data from the mobile health app, Releaf AppTM, through which 1,882 people tracked the effects of Cannabis flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post- administration symptom intensity levels, total dose used, and real-time side effect experiences.

The highs and the lows: Recreational marijuana laws and mental health treatment

Recreational marijuana laws (RMLs) continue to grow in popularity, but the effects on mental health treatment are unclear. This paper uses an event-study within a difference-in-differences framework to study the short-run impact of state RMLs on admissions into mental health treatment facilities. The results indicate that shortly after a state adopts an RML, they experience a decrease in the average number of mental health treatment admissions. The findings are driven by white, Black, and Medicaid-funded admissions and are consistent for both male and female admissions. The results are robust to alternative specifications and sensitivity analysis.

Cannabinoids: Emerging sleep modulator

Sleep is an essential biological phase of our daily life cycle and is necessary for maintaining homeostasis, alertness, metabolism, cognition, and other key functions across the animal kingdom. Dysfunctional sleep leads to deleterious effects on health, mood, and cognition, including memory deficits and an increased risk of diabetes, stroke, and neurological disorders. Sleep is regulated by several brain neuronal circuits, neuromodulators, and neurotransmitters, where cannabinoids have been increasingly found to play a part in its modulation. Cannabinoids, a group of lipid metabolites, are regulatory molecules that bind mainly to cannabinoid receptors (CB1 and CB2). Much evidence supports the role of cannabinoid receptors in the modulation of sleep, where their alteration exhibits sleep-promoting effects, including an increase in non-rapid-eye movement sleep and a reduction in sleep latency. However, the pharmacological alteration of CB1 receptors is associated with adverse psychotropic effects, which are not exhibited in CB2 receptor alteration. Hence, selective alteration of CB2 receptors is also of clinical importance, where it could potentially be used in treating sleep disorders. Thus, it is crucial to understand the neurobiological basis of cannabinoids in sleep physiology. In this review article, the alteration of the endocannabinoid system by various cannabinoids and their respective effects on the sleep-wake cycle are discussed based on recent findings. The mechanisms of the cannabinoid receptors on sleep and wakefulness are also explored for their clinical implications and potential therapeutic use on sleep disorders.

Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

The Impact Of Cannabidiol In Patients With Early Psychosis: A Randomized Controlled Trial

We aimed to study the effects of cannabidiol (CBD) in out-patients with early psychosis on clinical metrics of psychosis and cognition and on psychophysiological electroencephalogram (EEG) metrics of psychosis. Adult outpatient subjects with a primary psychotic disorder within approximately five years of psychosis onset were enrolled in a four-week, two-period, randomized, placebo-controlled crossover trial (clinicaltrials.gov NCT02504151). Subjects were randomized in a one-to-one ratio to receive either CBD (oral 800 mg/day) or placebo in the first of two treatment periods in a randomized, double-blind manner. Primary outcome measures assessed were psychosis symptoms measured using the Positive and Negative Syndrome Scale (PANSS); and cognition measured using the MATRICS Consensus Cognitive Battery (MCCB). Secondary clinical outcomes included Clinical Global Impression of Severity or of Improvement (CGI-S, CGI-I) and Quality of Life Scale (QLS). Statistical analyses were conducted using linear mixed models and nonparametric tests.

Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

Self-reported Medicinal Cannabis Use as an Alternative to Prescription and Over-the-counter Medication Use Among US Military Veterans

Mental and other physical health concerns and substance use disorder are common and co-occurring events experienced by US veterans. Treatment with medicinal cannabis is a potential alternative to unwanted medication use for veterans, but more clinical and epidemiologic research is needed to understand the risks and benefits. Data were collected from a cross-sectional, self-reported, anonymous survey asking US veterans about their health conditions, medical treatments, demographics, and medicinal cannabis use along with its self-reported effectiveness. In addition to descriptive statistics, logistic regression models were run to examine correlates of the use of cannabis as a substitution for prescription or over-the-counter medications.

Effects of CBD supplementation on ambulatory blood pressure and serum urotensin-II concentrations in Caucasian patients with essential hypertension: A sub-analysis of the HYPER-H21-4 trial

HYPER-H21–4 was a randomized crossover trial that aimed to determine if cannabidiol (CBD), a non-intoxicating constituent of cannabis, has relevant effects on blood pressure and vascular health in patients with essential hypertension. In the present sub-analysis, we aimed to elucidate whether serum urotensin-II concentrations may reflect hemodynamic changes caused by oral supplementation with CBD. The sub-analysis of this randomized crossover study included 51 patients with mild to moderate hypertension that received CBD for five weeks, and placebo for five weeks. After five weeks of oral CBD supplementation, but not placebo, serum urotensin concentrations reduced significantly in comparison to baseline (3.31 ± 1.46 ng/mL vs. 2.08 ± 0.91 ng/mL, P < 0.001). Following the five weeks of CBD supplementation, the magnitude of reduction in 24 h mean arterial pressure (MAP) positively correlated with the extent of change in serum urotensin levels (r = 0.412, P = 0.003); this association was independent of age, sex, BMI and previous antihypertensive treatment (β ± standard error, 0.023 ± 0.009, P = 0.009). No correlation was present in the placebo condition (r = −0.132, P = 0.357). In summary, potent vasoconstrictor urotensin seems to be implicated in CBD-mediated reduction in blood pressure, although further research is needed to confirm these notions.

The modulatory role of cannabis use in subconcussive neural injury

Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry

Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety. This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs. A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0.

Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios

As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = −4.709, d = 0.69, p = 2.41 × 10–5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.

Cannabinoids in hyperhidrosis

Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient’s quality of life using this novel low-cost and low-impact approach.