“Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.” https://www.ncbi.nlm.nih.gov/pubmed/19553915 “The surprising effect of cannabis on morphine dependence. Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth.” https://medicalxpress.com/news/2009-07-effect-cannabis-morphine.html
Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-Tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis
“The aim of the present study was to evaluate the efficacy of an oral formulation of Δ9-tetrahydrocannabinol (ECP002A) in patients with progressive multiple sclerosis (MS). Pain was significantly reduced when measured directly after administration of ECP002A in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo. Cognitive testing indicated that there was no decline in cognition after 2 or 4 weeks of treatment attributable to ECP002A compared with placebo. Implications This study specifically underlines the added value of thorough investigation of pharmacokinetic and pharmacodynamic associations in the target population. Despite the complex interplay of psychoactive effects and analgesia, the current oral formulation of Δ9-tetrahydrocannabinol may play a role in the treatment of spasticity and pain associated with MS because it was well tolerated and had a stable pharmacokinetic profile.” https://www.ncbi.nlm.nih.gov/pubmed/28189366]]>
Cannabinoids in treatment-resistant epilepsy: A review.
“Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative. Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD and diverse medical marijuana (MMJ) preparations containing: tetrahydrocannabinol (THC), CBD, and many other cannabinoids in differing combinations. These RCTs have studied the safety and explored the potential efficacy of CBD use in children with Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). The role of the placebo response is of paramount importance in studying medical cannabis products given the intense social and traditional media attention, as well as the strong beliefs held by many parents and patients that a natural product is safer and more effective than FDA-approved pharmaceutical agents. We lack valid data on the safety, efficacy, and dosing of artisanal preparations available from dispensaries in the 25 states and District of Columbia with MMJ programs and online sources of CBD and other cannabinoids. On the other hand, open-label studies with 100mg/ml CBD (Epidiolex®, GW Pharmaceuticals) have provided additional evidence of its efficacy along with an adequate safety profile (including certain drug interactions) in children and young adults with a spectrum of TREs. Further, Phase 3 RCTs with Epidiolex support efficacy and adequate safety profiles for children with DS and LGS at doses of 10- and 20-mg/kg/day. This article is part of a Special Issue titled “Cannabinoids and Epilepsy”.” https://www.ncbi.nlm.nih.gov/pubmed/28188044]]>
Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer
“Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer” http://www.ibtimes.com/can-marijuana-cure-cancer-pharmaceutical-company-developing-cannabis-medicine-treat-2489282
“GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of Concept Study in Glioma” http://ir.gwpharm.com/releasedetail.cfm?ReleaseID=1010672
“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials” http://labiotech.eu/gw-pharmaceuticals-brain-tumor/
“Drug Company Claims to Have Marijuana Treatment That Could Increase Lifespan of Brain Cancer Patients” http://www.complex.com/life/2017/02/gw-pharmaceuticals-claims-to-have-treatment-that-could-increase-lifespan-of-brain-cancer-patients
“GW Pharma’s cannabis-derived combo med helps brain cancer patients” http://www.fiercebiotech.com/biotech/gw-pharma-s-cannabis-derived-combo-med-helps-brain-cancer-patients
“GW pharmaceuticals to develop oncology portfolio after cannabis medication shows promising results” http://www.telegraph.co.uk/business/2017/02/07/gw-pharmaceuticals-develop-oncology-portfolio-cannabis-medication/
“GW Pharma is touting claims that a combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) produced positive survival benefits in a small study of 21 patients with recurrent glioblastoma multiforme, a common form of brain cancer.” https://endpts.com/gw-touts-positive-survival-benefit-in-small-brain-cancer-study-ablynx-files-for-ultra-rare-disease-drug-ok/
“GW Pharmaceuticals Is Set to Benefit as Cannabis Takes on Cancer” https://www.thestreet.com/story/13996559/1/gw-pharmaceuticals-is-set-to-benefit-as-cannabis-takes-on-cancer.html
“GW Pharmaceuticals Achieves Positive Results In Phase 2 Proof Of Concept Study In Glioma” https://www.clinicalleader.com/doc/gw-pharmaceuticals-phase-proof-of-concept-study-in-glioma-0001
“Here’s How Marijuana May Help Brain Cancer Patients Live Longer” http://www.menshealth.com/health/marijuana-drug-treats-brain-cancer?utm_source=facebook.com&utm_medium=social&utm_campaign=sharebutton
“New pharmaceutical drug uses marijuana to treat brain cancer” http://blog.sfgate.com/smellthetruth/2017/02/09/new-pharmaceutical-drug-uses-marijuana-to-treat-brain-cancer/
“Medicine’s Secret Weapon Against Brain Cancer Is Weed” https://www.inverse.com/article/27578-cancer-treatment-marijuana-gw-pharmaceuticals?utm_source=facebook.com&utm_medium=on_site&utm_campaign=desktop“The Next Big Brain Cancer Drug Could Come from Marijuana” http://fortune.com/2017/02/07/gw-pharmaceuticals-marijuana-brain-cancer/
“Can Weed Cure Cancer? Marijuana Helps Fight Glioblastoma Multiforme, One Of The Deadliest Forms Of Brain Cancer” http://www.medicaldaily.com/marijuana-just-might-help-cure-one-deadliest-forms-brain-cancer-410947 http://www.thctotalhealthcare.com/category/brain-cancer/Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.
“Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes.
The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury.
For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects.
New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.”
https://www.ncbi.nlm.nih.gov/pubmed/28161834
Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress.
“Social isolation stress (SIS) paradigm is a chronic stress procedure able to induce profound behavioral and neurochemical changes in rodents and evokes depressive and anxiety-like behaviors. Recent studies demonstrated that the cannabinoid system plays a key role in behavioral abnormalities such as depression through different pathways; however, there is no evidence showing a relation between SIS and the cannabinoid system. This study investigated the role of the cannabinoid system in depressive-like behavior and anxiety-like behavior of IC animals. Our findings suggest that the cannabinoid system is involved in depressive-like behaviors induced by SIS. We showed that activation of cannabinoid receptors (type 1 and 2) could mitigate depression-like behavior induced by SIS in a mouse model.” https://www.ncbi.nlm.nih.gov/pubmed/28161196]]>
A selective CB2R agonist (JWH133) restores neuronal circuit after Germinal Matrix Hemorrhage in the preterm via CX3CR1+ microglia.
“Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective.
We raise the hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates the CX3CR1+ microglia secreting neurotrophic factors and restores damaged neuronal circuit.
Overall, this study provides evidence that JWH133 promoted a neurotrophic phenotype of microglia (CX3CR1+ microglia), beyond merely alleviating microglial proliferation and inflammation.
Moreover, JWH133 restored impaired neuronal circuit, which represent a novel therapeutic strategy following GMH in clinic.”
https://www.ncbi.nlm.nih.gov/pubmed/28153531]]>
Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis.
“The elucidation of Δ9-tetrahydrocannabinol as the active principal of Cannabis sativa in 1963 initiated a fruitful half-century of scientific discovery, culminating in the identification of the endocannabinoid signaling system, a previously unknown neuromodulatory system. A primary function of the endocannabinoid signaling system is to maintain or recover homeostasis following psychological and physiological threats. We provide a brief introduction to the endocannabinoid signaling system and its role in synaptic plasticity. The majority of the article is devoted to a summary of current knowledge regarding the role of endocannabinoid signaling as both a regulator of endocrine responses to stress and as an effector of glucocorticoid and corticotrophin-releasing hormone signaling in the brain. We summarize data demonstrating that cannabinoid receptor 1 (CB1R) signaling can both inhibit and potentiate the activation of the hypothalamic-pituitary-adrenal axis by stress. We present a hypothesis that the inhibitory arm has high endocannabinoid tone and also serves to enhance recovery to baseline following stress, while the potentiating arm is not tonically active but can be activated by exogenous agonists. We discuss recent findings that corticotropin-releasing hormone in the amygdala enables hypothalamic-pituitary-adrenal axis activation via an increase in the catabolism of the endocannabinoid N-arachidonylethanolamine. We review data supporting the hypotheses that CB1R activation is required for many glucocorticoid effects, particularly feedback inhibition of hypothalamic-pituitary-adrenal axis activation, and that glucocorticoids mobilize the endocannabinoid 2-arachidonoylglycerol. These features of endocannabinoid signaling make it a tantalizing therapeutic target for treatment of stress-related disorders but to date, this promise is largely unrealized.” https://www.ncbi.nlm.nih.gov/pubmed/28134998]]>
Topical application of THC containing products is not able to cause positive cannabinoid finding in blood or urine.
“A male driver was checked during a traffic stop. A blood sample was collected 35min later and contained 7.3ng/mL THC, 3.5ng/mL 11-hydroxy-THC and 44.6ng/mL 11-nor-9-carboxy-THC. The subject claimed to have used two commercially produced products topically that contained 1.7ng and 102ng THC per mg, respectively. In an experiment, three volunteers (25, 26 and 34 years) applied both types of salves over a period of 3days every 2-4h. The application was extensive (50-100cm2). Each volunteer applied the products to different parts of the body (neck, arm/leg and trunk, respectively). After the first application blood and urine samples of the participants were taken every 2-4h until 15h after the last application (overall n=10 urine and n=10 blood samples, respectively, for each participant). All of these blood and urine samples were tested negative for THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC by a GC-MS method (LoD (THC)=0.40ng/mL; LoD (11-hydroxy-THC)=0.28ng/mL; LoD (THC-COOH)=1.6ng/mL;. LoD (THC-COOH in urine)=1.2ng/mL). According to our studies and further literature research on in vitro testing of transdermal uptake of THC, the exclusive application of (these two) topically applied products did not produce cannabinoid findings in blood or urine.” https://www.ncbi.nlm.nih.gov/pubmed/28122323]]>
Molecular Targets of the Phytocannabinoids: A Complex Picture.
“For centuries, hashish and marihuana, both derived from the Indian hemp Cannabis sativa L., have been used for their medicinal, as well as, their psychotropic effects.
These effects are associated with the phytocannabinoids which are oxygen containing C21 aromatic hydrocarbons found in Cannabis sativa L.
To date, over 120 phytocannabinoids have been isolated from Cannabis.
For many years, it was assumed that the beneficial effects of the phytocannabinoids were mediated by the cannabinoid receptors, CB1 and CB2. However, today we know that the picture is much more complex, with the same phytocannabinoid acting at multiple targets.
This contribution focuses on the molecular pharmacology of the phytocannabinoids, including Δ9-THC and CBD, from the prospective of the targets at which these important compounds act.”