Delta-8-tetrahydrocannabinol (Δ8THC) has been growing in popularity across the United States due to its reported therapeutic benefits, including pain relief, euphoria, relaxation, and mild psychoactive effects, especially in areas where sale of delta-9-tetrahydrocannabinol (Δ9THC) is illegal. Currently, much debate surrounds Δ8THC regarding its regulatory status and whether this compound is...
BACKGROUND: Mu opioid receptor (MOR) agonists are the primary medication class used to treat moderate to severe pain; however, the ongoing opioid overdose crisis underscores the need for alternatives to MOR agonists for pain treatment. Delta9-tetrahydrocannabinol (THC), a cannabinoid CB1 receptor (CB1R) agonist, and sigma1 receptor (σ1R) antagonists elicit antinociceptive effects albeit less...
Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), highlighting its structural characteristics, disease...
With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline. The current study was designed to determine how cannabis...
With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis...
Background: Ketamine is an anesthetic that has been proven to treat chronic pain via clinical trials; yet there is a gap in knowledge regarding the impact of the concomitant use of ketamine and cannabis on pain severity. This study examined cannabis consumers who participated in a pilot Ketamine-Assisted Psychotherapy (KAP) intervention study to examine pain severity. Methods: A subanalysis of...
Fatty acid binding protein 5 (FABP5) interacts with the endocannabinoid system in the brain via intracellular transport of anandamide, as well as Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. Previous work has established the behavioral effects of genetic deletion of FABP5, but not in the presence of THC. The present study sought to further elucidate the role of...
Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. We sought to characterize the pharmacokinetic and phenotypic profile of...
Salvinorin A (SalvA), the hallucinogenic derivative of the plant Salvia divinorum, is a selective κ-opioid receptor agonist that may also have antidepressant properties. Chronic mild stress (CMS) was applied to male and female Long-Evans rats to model anhedonia common in depression. The progressive loss in preference for a sucrose solution over plain water, a measure of anhedonia, and locomotor...
The structural basis to salvinorin A recognition of the kappa-opioid receptor is evaluated using a combination of site-directed mutagenesis and molecular-modeling techniques. The results show that salvinorin A recognizes a collection of residues in transmembrane II and VII, including Q115, Y119, Y313, I316, and Y320. The mutation of one hydrophobic residue in particular, I316, was found to...
Salvia divinorum and Mitragyna speciosa ("Kratom"), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the...
Data from clinical and preclinical studies converge implicating the plant-derived hallucinogen salvinorin A as an important pharmacologic tool; this psychoactive compound may expand scientific understandings on mammalian kappa-opioid receptor systems. Human salvinorin A effects, consistent with kappa-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted...
Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique structural and pharmacological properties. This non‐nitrogenous ligand lacks nearly all the structural features commonly associated with opioid ligand binding and selectivity. This study explores the structural basis to salvinorin A binding and selectivity using a combination of chimeric and single‐point mutant opioid...
Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally...
Kratom ( Mitragyna speciosa ) is a plant indigenous to Southeast Asia. This pilot study evaluated the pharmacodynamic (PD) effects, safety, and pharmacokinetics (PK) of kratom and several of its alkaloids. Recreational polydrug users (8 participants/cohort; 6 active: 2 placebo, N=40) completed the study. Participants had experience with opioids but were otherwise healthy. This study utilized a...