Cannabis is a complex plant, with major compounds such as delta-9- tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions. There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is...

Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9- tetrahydrocannabinol (Δ9_THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders. Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects. Cannabis can be detected in body...

Abstract Objectives: 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. Methods: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. Results: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is...

Background.—The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research....

Abstract Background Levels of cannabinoid 1 receptor (CB1R) mRNA and protein, which are expressed most heavily in the cholecystokinin class of GABA neurons, are lower in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia, and the magnitude of these differences is strongly correlated with that for glutamic acid decarboxylase (GAD67) mRNA, a synthesizing enzyme for GABA. However, whether this correlation reflects a cause-effect relationship is unknown. Methods Using quantitative in situ hybridization, we measured CB1R, GAD67, and diacylglycerol lipase alpha (DAGLα; the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically-engineered GAD67 heterozygous (GAD67+/−), CB1R heterozygous (CB1R+/−), CB1R knockout (CB1R−/−), and matched...

Chronic treatment with Δ 9 -tetrahydrocannabinol (THC) produces tolerance to cannabinoid-mediated behaviors and region-specific adaptation of brain cannabinoid receptors. However, the relationship between receptor adaptation and tolerance is not well understood, and the dose-response relationship of THC-induced cannabinoid receptor adaptation is unknown. This study assessed cannabinoid receptor function in the brain and cannabinoid-mediated behaviors after chronic treatment with different dosing regimens of THC. Mice were treated twice per day for 6.5 days with the following: vehicle, 10 mg/kg THC, or escalating doses of 10 to 20 to 30 or 10 to 30 to 60 mg/kg THC. Tolerance to cannabinoid-mediated locomotor inhibition, ring immobility, antinociception,...

Introduction: Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. Methods: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect...

Cannabis contains various cannabinoids, two of which have almost opposing actions: D9-tetrahydrocannabinol (D9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of D9-THC and CBD in 140 individuals. Three clear groups emerged: ‘THC only’, ‘THC+CBD’ and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

Background: While neuropsychological deficits have been reported in healthy individuals who use street cannabis, data in patients with multiple sclerosis (MS) are lacking. Given that MS is associated with cognitive deterioration, the aim of this study was to determine the neuropsychological effects of cannabis use in this population. Methods: Two groups, each of 25 patients with MS (cannabis users and nonusers), were administered the Minimal Assessment of Cognitive Function in MS battery of neuropsychological tests, the Hospital Anxiety and Depression Scale (HADS), and the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I). Group-matching and regression analysis were used to control for the...

Regular smoking of marijuana by itself causes visible and microscopic injury to the large airways that is consistently associated with an increased likelihood of symptoms of chronic bronchitis that subside after cessation of use. On the other hand, habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function when assessed either cross-sectionally or longitudinally, except for possible increases in lung volumes and modest increases in airway resistance of unclear clinical significance. Therefore, no clear link to chronic obstructive pulmonary disease has been established. Although marijuana smoke contains a number of carcinogens and cocarcinogens, findings from a limited number...