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Medical marijuana laws and adolescent use of marijuana and other substances: Alcohol, cigarettes, prescription drugs, and other illicit drugs

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Drug and Alcohol Dependence Home

“Historical shifts have taken place in the last twenty years in marijuana policy. The impact of medical marijuana laws (MML) on use of substances other than marijuana is not well understood. We examined the relationship between state MML and use of marijuana, cigarettes, illicit drugs, nonmedical use of prescription opioids, amphetamines, and tranquilizers, as well as binge drinking.

Among 8th graders, the prevalence of marijuana, binge drinking, cigarette use, non-medical use of opioids, amphetamines and tranquilizers, and any non-marijuana illicit drug use decreased after MML enactment.

Among 10th graders, the prevalence of substance use did not change after MML enactment.

Among 12th graders, non-medical prescription opioid and cigarette use increased after MML enactment.

Conclusions

MML enactment is associated with decreases in marijuana and other drugs in early adolescence in those states.

  • •Substance use decreased among 8th graders after medical marijuana use was legalized.
  • •Substance use did not change among 10th graders following legalization.
  • •Prescription drug and cigarette use increased among 12th graders after legalization.”

http://www.drugandalcoholdependence.com/article/S0376-8716(17)30569-0/abstract

From “Azalla” to Anandamide: Distilling the Therapeutic Potential of Cannabinoids

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Biological Psychiatry Home

“Cannabis has held a unique place in the hearts and minds of people since time immemorial: some have exalted its properties and considered it to be sacred; others have reviled it, considering it a root cause of social evil.

The Assyrians, who lived about 3000 years ago, documented the effects of cannabis on clay tablets. They referred to the plant according to its various uses: as “azalla,” when used as a medical agent; as hemp; and as “gan-zi-gun-nu”—“the drug that takes away the mind”   These seemingly contradictory properties—a substance that can be both a therapeutic agent and a corrupting psychoactive drug—have continued to puzzle us over the ensuing centuries.

As early as the 11th century, excessive cannabis use was suggested to be a cause of “moral degeneracy.”  On the other hand, the ostensible therapeutic value of cannabis was documented extensively in the early 19th century by Sir William B. O’Shaughnessy, an Irish physician working in Calcutta, India.

Given the critical role of the endocannabinoid system in modulating anxiety, it is clear that compounds that can modulate this system offer great promise as therapeutic agents for psychiatric disorders. It is therefore not surprising that the concept of medical marijuana is compelling to laypersons, clinicians, and researchers alike.

While there is not yet a robust body of literature supporting any specific psychiatric indication (despite the regulatory approval in some states of medical marijuana for specific psychiatric disorders), active lines of investigation of therapeutic targets within the endocannabinoid system offer hope for better treatment options.

The evidence at present suggests that the question of whether cannabinoids are good or bad is not dichotomous—it is likely both good and bad depending on the context of use, including dose, duration of exposure, and an individual’s genetic vulnerabilities. Therefore, the challenge that remains is to distill the good therapeutic effects of cannabinoids and thus weed out “gan-zi-gun-nu” from “azalla.””

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)32207-2/fulltext

 

Neuroprotective Properties of Endocannabinoids N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine Examined in Neuronal Precursors Derived from Human Pluripotent Stem Cells.

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Biochemistry (Moscow)

“Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1-10 µM range. However, both agents at 10 µM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/29223163

https://link.springer.com/article/10.1134%2FS0006297917110141

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 Value of Medical Marijuana in New Jersey Patients: A Community Partnership Research Endeavor.

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“The Public Health Program at Stockton University partnered with the Compassionate Care Foundation to ascertain the impact of medical marijuana on patients in New Jersey.

Results provide insight into the diagnoses for which patients used medical marijuana.

Results indicate increased mood, general overall condition, and energy as the highest consequences; level of pain in the middle range; and most frequent usage as 3 to 4 times a day. Repeated measures done after visit 2 showed eight statistically significant differences for patients after using medical marijuana: an increase in general quality of life, mobility, and mood, with a decrease in inflammation, intraocular pressure, spasms, seizures, and pain.

Results after visit 3 indicated seven significant differences compared to visit 1: decreased seizures, intraocular pressure, spasms, nausea, and pain, along with increased energy and mobility. No differences were found by patient diagnosis or age, but sex-related differences occurred in inflammation, mood, and energy.

Results support positive therapeutic benefits of medical marijuana, and despite methodological limitations, our study contributes to the growing body of literature.”

https://www.ncbi.nlm.nih.gov/pubmed/29202158

 

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

Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA).

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Journal of Pharmaceutical and Biomedical Analysis

“Hemp seed oil from Cannabis sativa L. is a very rich natural source of important nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes and cannabinoids, which contribute to the overall beneficial effects of the oil.

Hence, it is important to have an analytical method for the determination of these components in commercial samples. At the same time, it is also important to assess the safety of the product in terms of amount of any psychoactive cannabinoid present therein.

This work presents the development and validation of a highly sensitive, selective and rapid HPLC-UV method for the qualitative and quantitative determination of the main cannabinoids, namely cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidivarin (CBDV), present in 13 commercial hemp seed oils.

Moreover, since decomposition of cannabinoid acids generally occurs with light, air and heat, decarboxylation studies of the most abundant acid (CBDA) were carried out in both open and closed reactor and the kinetics parameters were evaluated at different temperatures in order to evaluate the stability of hemp seed oil in different storage conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/29182999
http://www.sciencedirect.com/science/article/pii/S0731708517322367?via%3Dihub

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges.

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“It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.].

These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS), a recently emerging regulator of several physiological processes.

The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc.

Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis) or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption.

Thus, the objective of the current article is (i) to summarize the most recent findings of the field; (ii) to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii) to identify open questions and key challenges; and (iv) to suggest promising future directions for cannabinoid-based drug development.”   https://www.ncbi.nlm.nih.gov/pubmed/29176975

“Although, many open questions await to be answered, pharmacological modulation of the (endo)cannabinoid signaling, and restoration of the homeostatic eCB tone of the tissues augur to be very promising future directions in the management of several pathological inflammation-accompanied diseases.”   https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full

Pharmacological Foundations of Cannabis Chemovars.

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“An advanced Mendelian Cannabis breeding program has been developed utilizing chemical markers to maximize the yield of phytocannabinoids and terpenoids with the aim to improve therapeutic efficacy and safety.

Cannabis is often divided into several categories based on cannabinoid content. Type I, Δ9-tetrahydrocannabinol-predominant, is the prevalent offering in both medical and recreational marketplaces. In recent years, the therapeutic benefits of cannabidiol have been better recognized, leading to the promotion of additional chemovars: Type II, Cannabis that contains both Δ9-tetrahydrocannabinol and cannabidiol, and cannabidiol-predominant Type III Cannabis.

While high-Δ9-tetrahydrocannabinol and high-myrcene chemovars dominate markets, these may not be optimal for patients who require distinct chemical profiles to achieve symptomatic relief. Type II Cannabis chemovars that display cannabidiol- and terpenoid-rich profiles have the potential to improve both efficacy and minimize adverse events associated with Δ9-tetrahydrocannabinol exposure. Cannabis samples were analyzed for cannabinoid and terpenoid content, and analytical results are presented via PhytoFacts, a patent-pending method of graphically displaying phytocannabinoid and terpenoid content, as well as scent, taste, and subjective therapeutic effect data.

Examples from the breeding program are highlighted and include Type I, II, and III Cannabis chemovars, those highly potent in terpenoids in general, or single components, for example, limonene, pinene, terpinolene, and linalool. Additionally, it is demonstrated how Type I - III chemovars have been developed with conserved terpenoid proportions. Specific chemovars may produce enhanced analgesia, anti-inflammatory, anticonvulsant, antidepressant, and anti-anxiety effects, while simultaneously reducing sequelae of Δ9-tetrahydrocannabinol such as panic, toxic psychosis, and short-term memory impairment.”

https://www.ncbi.nlm.nih.gov/pubmed/29161743

https://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-122240

Synthesis of Photoswitchable Δ9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling.

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Journal of the American Chemical Society

“The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nerv-ous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ9-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination. As such, azo-THCs enable CB1-mediated optical control of inwardly-rectifying potassium channels, as well as adenylyl cyclase.”

https://www.ncbi.nlm.nih.gov/pubmed/29161035

http://pubs.acs.org/doi/10.1021/jacs.7b06456