Detection of delta-9-tetrahydrocannabinol (THC) in oral fluid, blood and urine following oral consumption of low-content THC hemp oil.

 Forensic Science International

“Hemp-derivative (Cannabis sativa L.) food products containing trace levels of Δ-9-tetrahydrocannabinol (THC) are proposed for consumption in Australia and New Zealand; however, it is unclear whether use of these products will negatively affect existing drug screening protocols.

Consumption of low-content THC oil does not result in positive biological assessments.

It is therefore highly unlikely that ingestion of products containing these levels of THC will negatively impact existing region-specific drug driving enforcement protocols.”

https://www.ncbi.nlm.nih.gov/pubmed/29408718

https://www.sciencedirect.com/science/article/pii/S0379073817305492?via%3Dihub

CBD Enhances the Anticancer Effects of THC

Image result for molecular cancer therapeutics
“Δ9-Tetrahydrocannabinol (Δ9-THC) and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo.
Cannabidiol Enhances the Inhibitory Effects of  Δ9-Tetrahydrocannabinol on Human GlioblastomaCell Proliferation and Survival.
Δ9-THC and Cannabidiol Inhibit the Growth of Multiple Glioblastoma Cell Lines.
Cannabidiol Enhances the Inhibitory Effects of Δ9-THC on Glioblastoma Cell Growth.
Combination treatments with cannabinoids may improve overall efficacy”

“Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival”   http://mct.aacrjournals.org/content/9/1/180.full

Phytochemical Aspects and Therapeutic Perspective of Cannabinoids in Cancer Treatment

Cannabis sativa L. – dried pistillate inflorescences and trichomes on their surface. (a) dried pistillate inflorescences (50% of the size); (b) non‐cystolithic trichome; (c) cystolithic trichome; (d) capitate‐sessile trichome; (e) simple bulbous trichome; (f) capitate‐stalked trichome (400×).

“Cannabis sativa L. (Cannabaceae) is one of the first plants cultivated by man and one of the oldest plant sources of fibre, food and remedies.

Cannabinoids comprise the plant‐derived compounds and their synthetic derivatives as well as endogenously produced lipophilic mediators. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in CannabissativaL.

The principal active constituent is delta‐9‐tetrahydrocannabinol (THC), which binds to endocannabinoid receptors to exert its pharmacological activity, including psychoactive effect. The other important molecule of current interest is non‐psychotropic cannabidiol (CBD).

Since 1970s, phytocannabinoids have been known for their palliative effects on some cancer‐associated symptoms such as nausea and vomiting reduction, appetite stimulation and pain relief. More recently, these molecules have gained special attention for their role in cancer cell proliferation and death.

A large body of evidence suggests that cannabinoids affect multiple signalling pathways involved in the development of cancer, displaying an anti‐proliferative, proapoptotic, anti‐angiogenic and anti‐metastatic activity on a wide range of cell lines and animal models of cancer.”

https://www.intechopen.com/books/natural-products-and-cancer-drug-discovery/phytochemical-aspects-and-therapeutic-perspective-of-cannabinoids-in-cancer-treatment

Medical Cannabis for Neuropathic Pain.

Current Pain and Headache Reports

“Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications.

Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.

We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain.

These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.

Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain.

The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoidratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29388063

https://link.springer.com/article/10.1007%2Fs11916-018-0658-8

Cannabis Use, Lung Cancer, and Related Issues.

Image result for J Thorac Oncol.

“The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes with millions of regular users around the world.

The recreational use of cannabis is reflective of its neuropsychiatric effects such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment.

Increasing evidence supports cannabis in the management of chemotherapy induced nausea and vomiting and for pain management, but studies are limited particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products.

Smoking cannabis has not been proven to be a risk factor in the development of lung cancer but the data are limited by small studies, misclassification due to self-reporting of usage, small numbers of heavy cannabis smoking and confounding of risk associated with known causative agents for lung cancer such as parallel chronic tobacco use.

Cannabis and its biologically effective derivatives warrant additional research, ideally controlled trials where the CBD and the THC strength and usage are controlled and documented.”

https://www.ncbi.nlm.nih.gov/pubmed/29374567

“Good News: There’s No Definitive Link Between Marijuana Use and Lung Cancer” http://www.esquire.com/lifestyle/health/news/a52634/marijuana-lung-cancer/ 

“Study Shows No Proven Link Between Weed-Smoking and Lung Cancer”  http://www.complex.com/life/2017/01/weed-study-lung-cancer

Detection and Quantification of Cannabinoids in Extracts of Cannabis sativa Roots Using LC-MS/MS.

 

“A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)-trans9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa. Acetonitrile : methanol (80 : 20, v/v) was used for extraction; d3-cannabidiol and d3– tetrahydrocannabinol were used as the internal standards. All 10 cannabinoids showed a good regression relationship with r2 > 0.99. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in extracts of cannabis roots. To our knowledge, this is the first report for the quantification of cannabinoids in cannabis roots.”

https://www.ncbi.nlm.nih.gov/pubmed/29359294

https://www.thieme-connect.de/DOI/DOI?10.1055/s-0044-100798

Practical considerations in medical cannabis administration and dosing.

European Journal of Internal Medicine

“Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment.

With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable.

In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance.

CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks.

Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.”

PTL401, a New Formulation Based on Pro-nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers.

Journal of Pharmaceutical Sciences - JpharmSci Home

“There is growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive “first pass” metabolism.

A novel oral THC and CBD formulation, PTL401, utilizing an advanced self-emulsifying oral drug delivery system, was designed to circumvent the “first pass” effect. In this study, the bioavailability of THC and CBD from the PTL401 capsule was compared with similar doses from a marketed reference oromucosal spray (Sativex®).

No outstanding safety concerns were noted following either administration.

We conclude that PTL401 is a safe and effective delivery platform for both CBD and THC. The relatively faster absorption and improved bioavailability, compared to the oromucosal spray, justifies further, larger scale clinical studies with this formulation.”

Cannabidiol Does Not Convert to Δ9-Tetrahydrocannabinol in an In Vivo Animal Model.

Image result for Cannabis Cannabinoid Res. 2017 Dec 1

“Introduction: Cannabidiol (CBD) can convert to Δ9-tetrahydrocannabinol (THC) in vitro with prolonged exposure to simulated gastric fluid; however, in vitro conditions may not be representative of the in vivo gut environment. Using the minipig, we investigated whether enteral CBD converts to THC in vivo.

Conclusions: Findings of the present study show that orally dosed CBD, yielding clinically relevant plasma exposures, does not convert to THC in the minipig, a species predictive of human GI tract function.”

Decisive role of P42/44 mitogen-activated protein kinase in Δ9-tetrahydrocannabinol-induced migration of human mesenchymal stem cells.

Related image “In past years, medical interest in Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of the Cannabis plant, has been renewed due to the elucidation of the endocannabinoid system and diverse other receptor targets involved in biological cannabinoid effects.

The present study therefore investigates the impact of THC on the migration of mesenchymal stem cells (MSCs) which are known to be involved in various regenerative processes such as bone healing.

Collectively, this study demonstrates THC to exert a promigratory effect on MSCs via a CB1 receptor-dependent activation of p42/44 MAPK phosphorylation. This pathway may be involved in regenerative effects of THC and could be a target of pharmacological intervention.”   https://www.ncbi.nlm.nih.gov/pubmed/29285308

“Collectively and to the best of our knowledge, this is the first study reporting a promigratory impact of THC on MSCs, which may be an additional mechanism in the complex network of regenerative action of cannabinoids.”   http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22517&path[]=71182