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  • ∆9-tetrahydrocannabinol (THC), ∆9-tetrahydrocannabivarin (THCV), Cannabidiol (CBD), Cannabis, Intravenous
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Cannabis in the Arm: What Can we Learn from Intravenous Cannabinoid Studies?

Cannabis is widely used recreationally and for symptomatic relief in a number of ailments. However, cannabis has been implicated as a risk factor for the development of psychotic illness. For forty years researchers have utilised intravenous preparations of Δ(9)-THC, as well as several other phytocannabinoids, in a laboratory setting. The intravenous route has the most reliable pharmacokinetics, reducing inter-individual variation in bioavailability and is well suited for the delivery of synthetic compounds containing a sole pharmacological moiety. Given the association between cannabinoids and psychotic illness, there has been a resurgence of interest in experimental studies of cannabinoids in humans, and the intravenous route has...
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Cannabis Responsive Head Injury Induced Mutiple Disabilities: A Case Report

Abstract In recent years cannabinoids and their derivatives have drawn renewed attention because of their diverse pharmacologic activities. We report here one such case, where all types of medical & psychiatric treatment failed to improve the symptoms; however cannabis use was able to bring back this patient to normal productive & meaningful life. The patient was a 47 year old left handed Caucasian had minor subdural hematoma at the posterior vertex and a minor focal subarachnoid haemorrhage following a physical assault. His impairments included cognitive slowing with decreased short term memory, organized skill & language deficit. His physical disabilities included spastic gait (hemiplegic), VII...
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Cannabis, a complex plant: different compounds and different effects on individuals

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...
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Cannabinoids, cannabinoids and tinnitus

It has been hypothesized that tinnitus is a form of sensory epilepsy, arising partly from neuronal hyperactivity in auditory regions of the brain such as the cochlear nucleus and inferior colliculus. Although there is currently no effective drug treatment for tinnitus, anti-epileptic drugs are used in some cases as a potential treatment option. There is increasing evidence to suggest that cannabinoid drugs, i.e. cannabinoid receptor agonists, can also have anti-epileptic effects, at least in some cases and in some parts of the brain. It has been reported that cannabinoid CB1 receptors and the endogenous cannabinoid, 2-arachidonylglycerol (2-AG), are expressed in the cochlear nucleus and...
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Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana

The ATP-dependent drug efflux transporter P-glycoprotein (Pgp) plays a significant role in the absorption and disposition of many compounds. The purpose of this study was to investigate the possible interaction of P-gp with each of four major marijuana constituents: 9-tetrahydrocannabinol (THC), 11-nor-9-tetrahydrocannabinol-carboxylic acid (THC-COOH), cannabinol (CBN), and cannabidiol (CBD). The results of a P-gp ATPase activity screen showed that THC-COOH, CBN, THC, and CBD all stimulated P-gp ATPase activity with a Michaelis-Menten parameter (Vmax/Km) value of 1.3, 0.7, 0.1, and 0.05, respectively. Furthermore, CBD showed a concentration-dependent inhibitory effect on verapamil-stimulated ATPase activity with an IC50 value of 39.6 M, whereas all other tested...
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Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications

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...
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Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?

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...
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Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is...
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Clinical experiences with cannabinoids in spasticity management in multiple sclerosis

Introduction: Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Methods: Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor’s analysis and overall impression. Results: Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age of...
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Combined treatment with morphine and Δ9 -tetrahydrocannibinol (THC) in rhesus monkeys: antinociceptive tolerance and withdrawal

Abstract Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg Δ(9)-tetrahydrocannabinol (THC) twice daily; the antinociceptive effects (warm water tail withdrawal) of morphine, the cannabinoid receptor agonists WIN 55,212 [(R)-(1)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), and the κ opioid receptor agonist U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate) were examined before, during, and after treatment. To determine whether concurrent THC treatment...
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