Association between Marijuana Exposure and Pulmonary Function over 20 Years

We used repeated measurements of pulmonary function and smoking collected over 20 years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which was analyzed in parallel as a positive control. Conclusion: Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

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Bronchodilator Effect of Delta1-Tetrahydrocannabinol

Delta1-trans-tetrahydrocannabinol, (Delta1-THC) produces bronchodilatation in asthmatic patients. Administered in 63 microlitre metered volumes containing 50-200 micrograms by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.

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Cannabidiol and other Cannabinoids reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer's Disease

Alzheimer's disease (AD) is characterized by beta-amyloid (A-beta) deposition in senile plaques, neurofibrillary tangles, selective neuronal loss, and progressive cognitive deficits. Another invariant feature of the neurological disease is glial activation and is considered to be responsible of the ongoing inflammatory condition occurring in AD brain. In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.

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Cannabidiol as potential Anticancer Drug

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Delta9-tetrahydro-cannabinol (Delta9-THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Delta9-THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Delta9-THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents.

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Cannabinoid Facilitation of Fear Extinction Memory Recall in Humans

A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing.

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Cannabinoids in Health and Disease

Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists / antagonists / cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable.

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Chronic Adolescent Marijuana Use as a Risk Factor for Physical and Mental Health Problems in Young Adult Men

Some evidence suggests that youth who use marijuana heavily during adolescence may be particularly prone to health problems in later adulthood (e.g., respiratory illnesses, psychotic symptoms). However, relatively few longitudinal studies have prospectively examined the long-term physical and mental health consequences associated with chronic adolescent marijuana use. The present study used data from a longitudinal sample of Black and White young men to determine whether different developmental patterns of marijuana use, assessed annually from early adolescence to the mid-20s, were associated with adverse physical (e.g., asthma, high blood pressure) and mental (e.g., psychosis, anxiety disorders) health outcomes in the mid-30s. Analyses also examined whether chronic marijuana use was more strongly associated with later health problems in Black men relative to White men. Findings from latent class growth curve analysis identified 4 distinct subgroups of marijuana users: early onset chronic users, late increasing users, adolescence-limited users, and low/nonusers. Results indicated that the 4 marijuana use trajectory groups were not significantly different in terms of their physical and mental health problems assessed in the mid-30s. The associations between marijuana group membership and later health problems did not vary significantly by race. Findings are discussed in the context of a larger body of work investigating the potential long-term health consequences of early onset chronic marijuana use, as well as the complications inherent in studying the possible link between marijuana use and health effects.

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Clinical Endocannabinoid Deficiency (CECD)

This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.

 

Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.

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Clinical Endocannabinoid Deficiency (CECD) Revisited

A review of the literature indicates that significant progress has been made since Dr. Ethan B. Russo’s landmark paper, just ten years ago (February 2, 2004). Investigation at that time suggested that cannabinoids can block spinal, peripheral and gastrointestional mechanisms that promote pain in headache, fibromyalgia, irritable bowel syndrome and muscle spasm.

 

Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.

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Comparative Risk Assessment of Alcohol, Tobacco, Cannabis and other illicit Drugs

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations.

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