Our understanding of the Endocannabinoid System of animals, and its ubiquitous presence in nearly all members of Animalia, has opened the door to novel approaches targeting pain management, cancer therapeutics, modulation of neurologic disorders, stress reduction, anxiety management, and inflammatory diseases. Both endogenous and exogenous endocannabinoid-related molecules are able to function as direct ligands or, otherwise, influence the EndoCannabinoid System (ECS). This review article introduces the reader to the ECS in animals, and documents its potential as a source for emerging therapeutics.

Having chronic pain can make it difficult to sleep through the night. And having a lack of sleep can compound the effects of any health issue, leading to a vicious cycle. This study shows that moderate cannabis use can help to maintain sleep throughout the entire night for those with chronic pain.   Objectives Medical cannabis (MC) is increasingly being used for treatment of chronic pain symptoms. Among patients there is also a growing preference for the use of MC to manage sleep problems. The aim of the current study was to examine the associations between use of whole plant cannabis and sleep problems...

Background: It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. Methods: To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry. CB-receptor antagonists as well as a CRISPR double nickase knockdown approach were used to evaluate for receptor specificity of the observed proapoptotic...

Objective: Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. Methods: During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B...

Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte’s mother started adjunctive therapy with a high concentration cannabidiol/D9 -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte’s Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte’s seizure frequency from nearly 50 convulsive seizures per day to now 2–3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her...

Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to D9 -tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Methods: Materials included synthetic CBD, D8 -THC, and D9 -THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium...

Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OHDPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTPcS binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively...

The cannabinoid receptor agonist delta9 -tetrahydrocannabinol (THC) enhances the antinociceptive effects of mu opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on i.v. heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001–0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1–1.0 mg/kg) dosedependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032–0.032 mg/kg/infusion), heroin alone, or...

D9-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of D9-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this...

Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARc-activated pathway contributed to the antitumor effect of two cannabinoids, D9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activity and intracellular level of PPARc mRNA and protein, which was abolished by the PPARc inhibitor GW9662. Moreover, genetic ablation with small interfering RNA (siRNA), as well as pharmacological inhibition of PPARc decreased the cannabinoid-induced cell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCC tumors in mice. In addition, PPARc...