Abstract Background and Purpose Marijuana is the illicit drug most commonly used among pregnant and breastfeeding women. Different studies reported long-term adverse effects induced by in utero exposure to the main component of marijuana, Δ9-tetrahydrocannabinol (THC), both in rodents and in humans. However, little is known about any potential sex-dependent effects of marijuana consumption during pregnancy on newborns at early developmental ages. Experimental Approach We studied the effects of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN; 0.5 mg·kg−1 from GD5 to GD20) on the emotional reactivity and cognitive performance of male and female rat offspring from infancy through adolescence and tested the role of mGlu5 receptor...

Please use this link to access this publication. Abstract Synthetic cannabinoid receptor agonists (SCRAs) are an evolving class of new psychoactive substances (NPS) with structurally diverse compounds emerging each year. Due to the rapid pace at which these drugs enter the market, there is often little or nil information regarding the pharmacology of these substances despite widespread human use. In this study, 12 recently emerged SCRAs (reported between 2018 and 2020) were synthesized, analytically characterized, and pharmacologically evaluated using a live cell-based nanoluciferase complementation reporter assay that monitors in vitro cannabinoid receptor type 1 (CB1) activation via its interaction with β-arrestin 2 (βarr2). All synthesized SCRAs...

Abstract Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70–80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabinoid receptor 1 and 2 (CB1, CB2) constitute the basis of the endocannabinoid system. Interactions of cannabinoids with hypothalamic–pituitary–gonadal axis hormones are well documented, and two studies found a positive correlation between peak plasma endogenous cannabinoid anandamide with peak plasma 17β-estradiol, luteinizing hormone and follicle-stimulating hormone levels at ovulation in healthy premenopausal women. Do cannabinoids have an effect on HR+ BC? In this paper we review...

Please use this link to access this publication. Abstract Cannabinoids comprise a broad group of psychoactive substances that activate endogenous cannabinoid (EC) receptors (ie, CB1R and CB2R), altering neurotransmitter release in the brain. The importance of their regulatory role in different biological processes has prompted the development of synthetic cannabinoids (SCs), substantially more potent than tetrahydrocannabinol (THC, the main psychoactive substance of cannabis). Although SCs were primarily designed given their therapeutic applications, their recreational use has become a major public health concern due to several reports of severe intoxications and deaths. SCs have favored increased popularity over recent years due to their intensified psychoactive...

Abstract Background and Purpose Cannabis or cannabinoids produce characteristic tetrad effects—analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action. Experimental Approach We compared Δ9-tetrahydrocannabinol (Δ9-THC)-, WIN55212-2-, or XLR11-induced tetrad effects between wild-type (WT) and each genotype of CB1-, CB2- or GPR55-knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice. Key Results Systemic administration of Δ9-THC, WIN55212-2 or XLR11 produced dose-dependent tetrad effects in...

Abstract Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts...

Abstract Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the...

Please use this link to access this publication. Abstract The cannabinoid type 1 (CB1) receptor and the dopamine type 2 (D2) receptor are co-localized on medium spiny neuron terminals in the globus pallidus where they modulate neural circuits involved in voluntary movement. Physical interactions between the two receptors have been shown to alter receptor signaling in cell culture. The objectives of the current study were to identify the presence of CB1/D2 heteromers in the globus pallidus of C57BL/6J male mice, define how CB1/D2 heteromer levels are altered following treatment with cannabinoids and/or antipsychotics, and determine if fluctuating levels of CB1/D2 heteromers have functional consequences. Using in situ proximity ligation...

Abstract Aim To assess the efficacy, safety, and tolerability of oromucosal nabiximols cannabinoid medicine as adjunct therapy for children with spasticity due to cerebral palsy/traumatic central nervous system injury with inadequate response to existing treatment. Method Overall, 72 patients (mean [SD] age 12y 4mo [3y 1mo], range 8‒18y) were randomized at a ratio of 2:1 to receive nabiximols (n=47; 29 males, 18 females) or placebo (n=25; 15 males, 10 females) for 12 weeks (12 sprays/day max. based on clinical response/tolerability). The primary outcome was change from baseline in level of spasticity on a 0 to 10 Numerical Rating Scale (NRS), assessed by the primary caregiver...

Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing...