Tag Archives: THC

Cannabis Use, Lung Cancer, and Related Issues.

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“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.

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“A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)-trans-Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans-Δ8-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.

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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.”

https://www.ncbi.nlm.nih.gov/pubmed/29307505
http://www.ejinme.com/article/S0953-6205(18)30004-9/fulltext

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

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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.”

https://www.ncbi.nlm.nih.gov/pubmed/29287930
http://jpharmsci.org/article/S0022-3549(17)30890-0/pdf

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

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“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.”

 https://www.ncbi.nlm.nih.gov/pubmed/29285522

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

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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

HIV-infected cannabis users have lower circulating CD16+ monocytes and IP-10 levels compared to non-using HIV patients.

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“Chronic immune activation and elevated numbers of circulating activated monocytes (CD16) are implicated in HIV-associated neuroinflammation.

The objective was to compare the level of circulating CD16 monocytes and interferon-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and non-cannabis users (HIV+MJ-), and determine whether in vitro Δ-Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression as well as IP-10 production by monocytes.

RESULTS:

HIV+MJ+ donors possessed a lower level of circulating CD16 monocytes and serum IP-10, compared to HIV+MJ- donors. Further, monocytes from HIV+MJ+ donors were unable to induce CD16 expression when treated with in vitro IFNα, while HIV-MJ- and HIV+MJ- donors displayed pronounced CD16 induction, suggesting anti-inflammatory effects by cannabis.

CONCLUSIONS:

Components of cannabis, including THC, may decelerate peripheral monocyte processes that are implicated in HIV-associated neuroinflammation.”   https://www.ncbi.nlm.nih.gov/pubmed/29194121

http://journals.lww.com/aidsonline/Abstract/publishahead/HIV_infected_cannabis_users_have_lower_circulating.97348.aspx

“Medical Cannabis May Improve Neurocognitive Disorder in Patients With HIV. Medical marijuana could help prevent the development of neurocognitive disorders in patients with HIV, according to a new study. Tetrahydrocannabinol (THC), the prominent compound in marijuana, was found to slow the process of neurodegeneration — a condition common in about half of all patients with HIV — according to a study from researchers at Michigan State University (MSU).” https://www.specialtypharmacytimes.com/news/medical-cannabis-may-improve-neurocognitive-disorder-in-patients-with-hiv

“Marijuana may help HIV patients keep mental stamina longer. Norbert Kaminski, director of Michigan State University‘s Institute for Integrative Toxicology, has found that a chemical in marijuana, known as THC, can potentially slow the process of mental decline that can occur in up to 50 percent of HIV patients.” https://medicalxpress.com/news/2017-12-marijuana-hiv-patients-mental-stamina.html

“New Research Says A Chemical in Marijuana May Help HIV Patients Maintain Their Mental Fortitude. “The patients who didn’t smoke marijuana had a very high level of inflammatory cells compared to those who did use. In fact, those who used marijuana had levels pretty close to a healthy person not infected with HIV.”” http://game360.co/2017/12/new-research-says-chemical-marijuana-may-help-hiv-patients-maintain-mental-fortitude/

“Cannabis could prevent mental decline in up to 50 percent of HIV sufferers, new research reveals. Patients who use marijuana have fewer inflammatory white blood cells, which are involved in the immune system, a study found. This could save infected people from mental decline, which affects up to 50 percent of sufferers due to ongoing inflammation in the brain as a result of the immune system constantly fighting the virus. Lead author Professor Norbert Kaminski from Michigan State University, said: ‘Those who used marijuana had [inflammatory cell] levels pretty close to a healthy person not infected with HIV.'” http://www.dailymail.co.uk/health/article-5174379/Cannabis-prevent-mental-decline-HIV-sufferers.html

“Marijuana may help increase mental strength in HIV patients”  http://www.timesnownews.com/health/article/marijuana-may-help-increase-mental-strength-in-hiv-patients/145504

Bioactive products from singlet oxygen photooxygenation of cannabinoids.

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European Journal of Medicinal Chemistry

“Photooxygenation of Δ8 tetrahydrocannabinol (Δ8-THC), Δ9 tetrahydrocannabinol (Δ9-THC), Δ9 tetrahydrocannabinolic acid (Δ9-THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides.

Testing these compounds for their modulatory effect on cannabinoid receptors CB1 and CB2 led to the identification of 7 and 21 as CB1 partial agonists with Ki values of 0.043 μM and 0.048 μM, respectively and 23 as a cannabinoid with high binding affinity for CB2 with Ki value of 0.0095 μM, but much less affinity towards CB1 (Ki 0.467 μM).

The synthesized compounds showed cytotoxic activity against cancer cell lines (SK-MEL, KB, BT-549, and SK-OV-3) with IC50 values ranging from 4.2 to 8.5 μg/mL.

Several of those compounds showed antimicrobial, antimalarial and antileishmanial activities, with compound 14 being the most potent against various pathogens.”

https://www.ncbi.nlm.nih.gov/pubmed/29232588

http://www.sciencedirect.com/science/article/pii/S0223523417309467?via%3Dihub

Therapeutic use of Δ9-THC and cannabidiol: evaluation of a new extraction procedure for the preparation of cannabis-based olive oil.

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“Since 2013 Cannabis-based preparations, containing the two main cannabinoids of interest, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD), can be used for therapeutic purposes, such as palliative care, neurodegenerative disorder treatment and other therapies.

The preparations may consist of a drug partition in sachets, capsules or through the extraction in certified olive oil.

OBJECTIVE:

the aims of the study were: a) to develop and validate a new liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the identification and quantification of THC and CBD in olive oil; b) to evaluate the extraction efficiency and reproducibility of a new commercial extractor on the market.

METHODS:

the olive oil was simply diluted three consecutive times, using organic solvents with increasing polarity index (n-hexane → isopropanol → methanol). The sample was then direct injected into LC-MS/MS system, operating in Multiple Reaction Monitoring Mode, in positive polarization. The method was then fully validated.

RESULTS:

The method assessed to be linear over the range 0.1-10 ng/µL for both THC and CBD. Imprecision and accuracy were within 12.2% and 16.9% respectively; matrix effects proved to be negligible; THC concentration in oil is stable up to two months at room temperature, whenever kept in the dark. CBD provided a degradation of 30% within ten weeks. The method was then applied to olive oil after sample preparation, in order to evaluate the efficiency of extraction of a new generation instrument. Temperature of extraction is the most relevant factor to be optimized. Indeed, a difference of 2 °C (from 94.5°C to 96.5°C, the highest temperature reached in the experiments) of the heating phase, increases the percentage of extraction from 54.2% to 64.0% for THC and from 58.2% to 67.0% for CBD. The amount of THC acid and CBD acid that are decarboxylated during the procedure must be check out in the future.

CONCLUSION:

the developed method was simple and fast. The extraction procedure proved to be highly reproducible and applicable routinely to cannabis preparations.”

https://www.ncbi.nlm.nih.gov/pubmed/29189144

http://www.eurekaselect.com/157854/article

“Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil Preparations.”  https://www.ncbi.nlm.nih.gov/pubmed/29202510

Antinociceptive effects of mixtures of mu opioid receptor agonists and cannabinoid receptor agonists in rats: impact of drug and fixed-dose ratio.

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“Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists).

Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments.

The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Δ9-THC and CP55940 were studied in male Sprague-Dawley rats (n=16) using a warm water tail withdrawal procedure.

The ratio of opioid to cannabinoid (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Δ9-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture.

The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29183835

http://www.sciencedirect.com/science/article/pii/S0014299917307719