Abstract Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in...

Abstract   Background: This study is based on the premise that while consumption of cannabis has increased for medicinal and recreational purposes there has also been an increase in adverse events seemingly associated with cannabis usage.   Objective: This study was designed to investigate the effect of different concentrations of Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) separately and in combination on blood flow.   Method: Forty male Sprague-Dawley rats were randomly divided into eight groups consisting of five rats each. Six of the test groups received different concentrations of THC and CBD (1 and 2 mg/kg body weight) respectively, while the seventh group received an extract with a...

Abstract Multiple sclerosis (MS) is the most common cause of non-traumatic neurological disability in young adults. It has effects at different levels: physical, emotional, psychological, cognitive and social, with a great variety of signs and symptoms. In particular, spasticity contributes to reducing the motor performance of patients with MS, causing pain, reduction in distance walked and limitations in social life. We present the case of a 39-year-old woman with MS. She was treated with delta-9-tetrahydrocannabinol/cannabidiol and the outcome was assessed with the International Classification of Functioning Disability and Health core set framework. LEARNING POINTS The clinical presentation of multiple sclerosis (MS) is heterogeneous but...

ABSTRACT Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (−)-trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.

Abstract Graft-versus-host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments. In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R), which is expressed on nearly all immune cells, and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells or administration of a selective CB2R pharmacological antagonist exacerbated acute GVHD lethality. This was accompanied primarily by the expansion of proinflammatory CD8+ T cells, indicating that constitutive CB2R expression on T cells...

Abstract Cannabis consumption is increasing worldwide either for recreational or medical purposes. Its use during gestation is associated with negative pregnancy outcomes such as, intrauterine growth restriction, preterm birth, low birth weight, and increased risk of miscarriage, though the underlying molecular mechanisms are unknown. Cannabis sativa main psychoactive compound, Δ9-tetrahydrocannabinol (THC) is highly lipophilic, and as such, readily crosses the placenta. Consequently, THC may alter normal placental development and function. Here, we hypothesize alterations of placental steroidogenesis caused by THC exposure. The impact on placental estrogenic signaling was examined by studying THC effects upon the enzyme involved in estrogens production, aromatase and on estrogen receptor α...

Abstract Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2...

Abstract Background Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical need. We hypothesized that cannabis reduces neuropathic pain by reducing functional coupling in the raphe nuclei. Methods We assessed the impact of inhalation of vaporized cannabis plant (containing 10.3% Δ9-tetrahydrocannabinol/0.05% cannabidiol) or placebo cannabis on brain resting-state blood oxygen level–dependent functional connectivity and pain behavior induced by paclitaxel in rats. Rats received paclitaxel to produce chemotherapy-induced peripheral neuropathy or its vehicle. Behavioral and imaging experiments were performed after neuropathy was established and stable. Images were registered to, and analyzed using, a 3D magnetic resonance imaging rat atlas providing site-specific data on more than 168 different brain areas. Results Prior to vaporization, paclitaxel...

Abstract Cannabis has been used for both recreational and medicinal purposes for more than 4 millennia. Cannabis has been studied in various medical disorders including neurological disorders. There are well-known risks of long-term use of cannabis, including low motivation, lowered cognitive capabilities, and diminished IQ and brain mass. Cannabinoids are compounds in cannabis that are known to have therapeutic potential. The most abundant chemicals in cannabinoids are delta-9-tetrahydrocannabinol and cannabidiol. Delta-9-tetrahydrocannabinol has psychotropic effects that limits its use as a pharmacotherapeutic agent. Cannabidiol is a nonpsychotropic chemical and therefore has become a compound of interest for clinical researchers to study its therapeutic potential. This...

Abstract Drugs of abuse induce cell type specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), that can bias signaling towards D1-MSNs and enhance relapse vulnerability. Whether ∆9-tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC+cannabidiol (THC+CBD). After extinction training spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC+CBD induced a loss of large spine heads in D1- but not D2-MSNs and commensurate reductions in glutamate synaptic transmission. Also, presynaptic CB1R function was impaired selectively at...