THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans

Posted on September 2, 2017 by David Worrell

“Cannabidiol (CBD) is a cannabinoid of the cannabis plant devoid of intoxicating effects. It may be of therapeutic value in a large number of diseases, including epilepsy, anxiety disorders, depression, schizophrenic psychosis, inflammatory diseases, dystonia, nausea, and vomiting without causing relevant or severe side effects. No biosynthetic enzyme or pathway exists in the human body to convert CBD to THC. This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.” https://www.ncbi.nlm.nih.gov/pubmed/28861499 http://online.liebertpub.com/doi/full/10.1089/can.2016.0036 “A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.” https://www.ncbi.nlm.nih.gov/pubmed/28861507]]>

Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

Posted on August 31, 2017 by David Worrell

“Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing, and storage. While the biological effects of decarboxylated cannabinoids such as Δ⁹ -tetrahydrocannabinol (Δ⁹ -THC) have been extensively investigated, the bioactivity of Δ⁹ -THCA is largely unknown, despite its occurrence in different Cannabis preparations. The aim of this study was to determine whether Δ⁹ -THCA modulates the PPARγ pathway and has neuroprotective activity. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ⁹ -THCA on mitochondrial biogenesis and PGC-1α expression was investigated in N2a cells. The neuroprotective effect was analysed in STHdh^Q111/Q111 cells expressing a mutated form of the huntingtin protein, and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). In vivo neuroprotective activity of Δ⁹ -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NP).

KEY RESULTS:

Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ⁹ -THCA increases mitochondrial mass in neuroblastoma N2a cells, and prevents cytotoxicity induced by serum deprivation in STHdh^Q111/Q111cells and by mutHtt-q94 in N2a cells. Δ⁹ -THCA, through a PPARγ-dependent pathway, was neuroprotectant in mice intoxicated with 3-NP, improving motor deficits and preventing striatal degeneration. In addition, Δ⁹ -THCA attenuated microgliosis, astrogliosis and the upregulation of proinflammatory markers induced by 3-NP.

CONCLUSION AND IMPLICATIONS:

Δ⁹ -THCA shows potent neuroprotective activity, worth consideration for the treatment of Huntington´s Disease and possibly other neurodegenerative and neuroinflammatory diseases.” https://www.ncbi.nlm.nih.gov/pubmed/28853159 http://onlinelibrary.wiley.com/doi/10.1111/bph.14019/abstract]]>

Interaction between Cannabinoid Type 1 and Type 2 Receptors in the Modulation of Subventricular Zone and Dentate Gyrus Neurogenesis.

Posted on August 31, 2017 by David Worrell

“Neurogenesis in the adult mammalian brain occurs mainly in two neurogenic niches, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus (DG). Cannabinoid type 1 and 2 receptors (CB₁R and CB₂R) have been shown to differently modulate neurogenesis. However, low attention has been given to the interaction between CB₁R and CB₂R in modulating postnatal neurogenesis (proliferation, neuronal differentiation and maturation). We focused on a putative crosstalk between CB₁R and CB₂R to modulate neurogenesis and cultured SVZ and DG stem/progenitor cells from early postnatal (P1-3) Sprague-Dawley rats. Data showed that the non-selective cannabinoid receptor agonist WIN55,212-2 promotes DG cell proliferation (measured by BrdU staining), an effect blocked by either CB₁R or CB₂R selective antagonists. Experiments with selective agonists showed that facilitation of DG cell proliferation requires co-activation of both CB₁R and CB₂R. Cell proliferation in the SVZ was not affected by the non-selective receptor agonist, but it was enhanced by CB₁R selective activation. However, either CB₁R or CB₂R selective antagonists abolished the effect of the CB₁R agonist in SVZ cell proliferation. Neuronal differentiation (measured by immunocytochemistry against neuronal markers of different stages and calcium imaging) was facilitated by WIN55,212-2 at both SVZ and DG. This effect was mimicked by either CB₁R or CB₂R selective agonists and blocked by either CB₁R or CB₂R selective antagonists, cross-antagonism being evident. In summary, our findings indicate a tight interaction between CB₁R and CB₂R to modulate neurogenesis in the two major neurogenic niches, thus contributing to further unraveling the mechanisms behind the action of endocannabinoids in the brain.”

https://www.ncbi.nlm.nih.gov/pubmed/28848435

http://journal.frontiersin.org/article/10.3389/fphar.2017.00516/full

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Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium.

Posted on August 31, 2017 by David Worrell

“Cannabinoids, as multi‑target mediators, activate cannabinoid receptors and transient receptor potential vanilloid (TRPV) channels. There is evidence to support a functional interaction of cannabinoid receptors and TRPV channels when they are coexpressed. Human conjunctiva demonstrates widespread cannabinoid receptor type 1 (CB1), CB2 and TRPV channel localization. The aim of the present study was to investigate the expression profile for cannabinoid receptors (CB1 and CB2) and TRPV channels in pterygium, an ocular surface lesion originating from the conjunctiva. The differentiated expression of cannabinoid receptors in combination with the presence of TRPV channels, in primary and recurrent pterygia, imply a potential role of these cannabinoidtargets in the underlying mechanisms of pterygium.”

https://www.ncbi.nlm.nih.gov/pubmed/28849159

https://www.spandidos-publications.com/10.3892/mmr.2017.7246

“A pterygium is a pinkish, triangular tissue growth on the cornea of the eye.” https://en.wikipedia.org/wiki/Pterygium_(conjunctiva)

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Cannabis use is associated with a substantial reduction in premature deaths in the United States.

Posted on August 29, 2017 by David Worrell

“Adverse effects of moderate Cannabis use on physical health are subtle and rarely fatal, while Cannabis use is associated with decreased rates of obesity, diabetes mellitus, mortality from traumatic brain injury, use of alcohol and prescription drugs, driving fatalities, and opioid overdose deaths.

These data suggest that Cannabis use may decrease premature deaths.

To date, no studies have attempted to estimate impacts of Cannabis use on premature death that include both adverse and beneficial effects on physical health. Marijuana use is estimated to reduce premature deaths from diabetes mellitus, cancer, and traumatic brain injury by 989 to 2,511 deaths for each 1% of the population using Cannabis. The analysis predicts an estimated 23,500 to 47,500 deaths prevented annually if medical marijuana were legal nationwide. A number of other potential causes of reduced mortality due to Cannabis use were revealed, but were excluded from the analysis because quantitative data were lacking. These estimates thus substantially underestimate the actual impact of Cannabis use on premature death.

Overall, prohibition is estimated to lead to similar numbers of premature deaths as drunk driving, homicide, or fatal opioid overdose. Cannabis use prevents thousands of premature deaths each year, and Cannabis prohibition is revealed as a major cause of premature death in the U.S.”

https://scholarworks.iu.edu/dspace/handle/2022/21632

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Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors and relevance for Alzheimer's disease and levodopa-induced dyskinesia.

Posted on August 29, 2017 by David Worrell

“Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB₁ and CB₂ receptors, which may form heteromeric complexes (CB₁-CB₂Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoidreceptors in resting and LPS/IFN-γ-activated microglia. Unlike CB₁, CB₂ receptors and CB₁-CB₂Hets were upregulated in activated microglia. Resting cell refractory CB₂ receptors became robustly coupled to G_i in activated cells, in which CB₁-CB₂Hets mediated a positive cross-talk. Resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß_1-42). Activation microglial markers were detected in the striatum of a Parkinson’s disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APP_Sw,Ind) mice, a transgenic Alzheimer’s disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APP_Sw,Ind and in cells from control animals activated using LPS plus IFN- γ. Expression of CB₁-CB₂Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment. In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB₁-CB₂Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB₁-CB₂ heteroreceptor complex in activated microglia have potential as targets in the treatment of neurodegenerative diseases.” https://www.ncbi.nlm.nih.gov/pubmed/28843453 http://www.sciencedirect.com/science/article/pii/S0889159117304038]]>

Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors and relevance for Alzheimer’s disease and levodopa-induced dyskinesia.

Posted on August 29, 2017 by David Worrell

Cover image

We aimed at establishing the expression and signaling properties of cannabinoidreceptors in resting and LPS/IFN-γ-activated microglia. Unlike CB₁, CB₂ receptors and CB₁-CB₂Hets were upregulated in activated microglia. Resting cell refractory CB₂ receptors became robustly coupled to G_i in activated cells, in which CB₁-CB₂Hets mediated a positive cross-talk. Resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß_1-42). Activation microglial markers were detected in the striatum of a Parkinson’s disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APP_Sw,Ind) mice, a transgenic Alzheimer’s disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APP_Sw,Ind and in cells from control animals activated using LPS plus IFN- γ. Expression of CB₁-CB₂Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment.

In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB₁-CB₂Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB₁-CB₂ heteroreceptor complex in activated microglia have potential as targets in the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28843453

http://www.sciencedirect.com/science/article/pii/S0889159117304038

The potential role of cannabinoids in epilepsy treatment.

Posted on August 29, 2017 by David Worrell

“Epilepsy is one of the world’s oldest recognized and prevalent neurological diseases. It has a great negative impact on patients’ quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs’ side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system. Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.” https://www.ncbi.nlm.nih.gov/pubmed/28845714 http://www.tandfonline.com/doi/abs/10.1080/14737175.2017.1373019

“The role of cannabinoids and endocannabinoid system in the treatment of epilepsy. Cannabis has been used for thousands of years in the treatment of various diseases. Cannabinoids have been shown in preliminary animal model studies and in studies of patients with epilepsy to have antiepileptic activity. ” https://www.degruyter.com/view/j/joepi.ahead-of-print/joepi-2015-0034/joepi-2015-0034.xml

“Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25475762

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Cannabinoids as Anticancer Drugs.

Posted on August 23, 2017 by David Worrell

“The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.” https://www.ncbi.nlm.nih.gov/pubmed/28826542 http://www.sciencedirect.com/science/article/pii/S105435891730039X?via%3Dihub]]>

Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

Posted on August 23, 2017 by David Worrell

“The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam’s professed “pharmacological treasure trove.”” https://www.ncbi.nlm.nih.gov/pubmed/28826544 http://www.sciencedirect.com/science/article/pii/S1054358917300273?via%3Dihub]]>