Effort-related decision making and cannabis use among college students

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“Cannabis exerts an indirect effect on dopamine (DA) output in the mesolimbic projection, a circuit implicated in reward processing and effort expenditure, and thus may be associated with aberrant effort-based decision making. The “amotivation syndrome” hypothesis suggests that regular cannabis use results in impaired capacity for goal-directed behavior. However, investigations of this hypothesis have used divergent methodology and have not controlled for key confounding variables.

The present study extends these findings by examining the relation between cannabis use and effort-related decision making in a sample of college students. Cannabis using (n = 25; 68% meeting criteria for Cannabis Use Disorder) and noncannabis using (n = 22) students completed the Effort Expenditure for Rewards Task (EEfRT). In generalized estimating equation models, reward magnitude, reward probability, and expected value predicted greater likelihood of selecting a high-effort trial. Furthermore, past-month cannabis days and cannabis use disorder symptoms predicted the likelihood of selecting a high-effort trial, such that greater levels of both cannabis use days and symptoms were associated with an increased likelihood after controlling for Attention Deficit/Hyperactivity Disorder (ADHD) symptoms, distress tolerance, income, and delay discounting.

The results provide preliminary evidence suggesting that college students who use cannabis are more likely to expend effort to obtain reward, even after controlling for the magnitude of the reward and the probability of reward receipt. Thus, these results do not support the amotivational syndrome hypothesis. Future research with a larger sample is required to evaluate possible associations between cannabis use and patterns of real-world effortful behavior over time.”

https://pubmed.ncbi.nlm.nih.gov/35084912/

“Cannabis use is becoming increasingly tolerated, both culturally and legally; yet, the risks associated with cannabis use are still unclear. There is a perception among the general public that cannabis leads to amotivation and diminished effortful behavior. Our results do not support the amotivational hypothesis but, instead, that cannabis use is associated with a greater likelihood of selecting high effort trials.”

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000544

The Impact of Isolated Baseline Cannabis Use on Outcomes Following Thoracolumbar Spinal Fusion: A Propensity Score-Matched Analysis

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“Background: There is limited literature evaluating the impact of isolated cannabis use on outcomes for patients following spinal surgery. This study sought to compare 90-day complication, 90-day readmission, as well as 2-year revision rates between baseline cannabis users and non-users following thoracolumbar spinal fusion (TLF) for adult spinal deformity (ASD).

Results: 704 patients were identified (n=352 each), with comparable age, sex, race, primary insurance, Charlson/Deyo scores, surgical approach, and levels fused between cohorts (all, p>0.05). Cannabis users (versus non-users) incurred lower 90-day overall and medical complication rates (2.4% vs. 4.8%, p=0.013; 2.0% vs. 4.1%, p=0.018). Cohorts had otherwise comparable complication, revision, and readmission rates (p>0.05). Baseline cannabis use was associated with a lower risk of 90-day medical complications (OR=0.47, p=0.005). Isolated baseline cannabis use was not associated with 90-day surgical complications and readmissions, or two-year revisions.

Conclusion: Isolated baseline cannabis use, in the absence of any other diagnosed substance abuse disorders, was not associated with increased odds of 90-day surgical complications or readmissions or two-year revisions, though its use was associated with reduced odds of 90-day medical complications when compared to non-users undergoing TLF for ASD. Further investigations are warranted to identify the physiologic mechanisms underlying these findings. Level of Evidence: III.”

https://pubmed.ncbi.nlm.nih.gov/35821925/

“Compared to patients with ASD who underwent TLF without baseline cannabis use, patients with isolated baseline cannabis use were found to have no increase in odds of incurring 90-day surgical complications or readmissions or revisions two years postoperatively, though reduced odds of experiencing 90-day medical complications were observed.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210439/

Cannabidiol-Treated Ovariectomized Mice Show Improved Glucose, Energy, and Bone Metabolism With a Bloom in Lactobacillus

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“Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed.

Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice.

We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-treated OVX mice had increased relative abundance of fecal Lactobacillus species and several gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption.

These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.”

https://pubmed.ncbi.nlm.nih.gov/35800441/

“In conclusion, our results indicate that CBD treatment of OVX mice impacts the immune system and the gut microbiota to improve energy metabolism and bone homeostasis. These data indicate that CBD modulates a gut-bone axis to favorably alleviate several chronic disease symptoms of postmenopause.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.900667/full

Cannabis: Chemistry, extraction and therapeutic applications

Chemosphere

“Cannabis, a genus of perennial indigenous plants is well known for its recreational and medicinal activities. Cannabis and its derivatives have potential therapeutic activities to treat epilepsy, anxiety, depression, tumors, cancer, Alzheimer’s disease, Parkinson’s disease, to name a few.

This article reviews some recent literature on the bioactive constituents of Cannabis, commonly known as phytocannabinoids, their interactions with the different cannabinoids and non-cannabinoid receptors as well as the significances of these interactions in treating various diseases and syndromes.

The biochemistry of some notable cannabinoids such as tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene and their carboxylic acid derivatives is explained in the context of therapeutic activities.

The medicinal features of Cannabis-derived terpenes are elucidated for treating several neuro and non-neuro disorders. Different extraction techniques to recover cannabinoids are systematically discussed. Besides the medicinal activities, the traditional and recreational utilities of Cannabis and its derivatives are presented. A brief note on the legalization of Cannabis-derived products is provided.

This review provides comprehensive knowledge about the medicinal properties, recreational usage, extraction techniques, legalization and some prospects of cannabinoids and terpenes extracted from Cannabis.”

https://pubmed.ncbi.nlm.nih.gov/34838836/

“Cannabinoids have therapeutic effects against various health disorders.•

Medicinal effects are due to the interactions of cannabinoids with bio-receptors.•

Cannabinoids can be extracted from Cannabis plant products by eco-friendly extraction methods.”

https://www.sciencedirect.com/science/article/abs/pii/S0045653521034846?via%3Dihub

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[GPR18 receptor – the structure and the role in the physiology and pathophysiology]

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“G-protein coupled receptors constitute the largest family of membrane receptors and they participate in the maintenance of the homeostasis in the body. Some of these receptors still remain orphan receptors as there is insufficient research and ambiguous evidence concerning their function and endogenous ligands.

For a long time, GPR18 belonged to this group, but recently it has been classified as an endocannabinoid receptor due to its affinity to cannabinoid ligands.

GPR18 receptor is expressed in the encephalon, thyroid gland, leukocytes, lungs and testicles. The modulatory role of GPR18 receptor has been proven in the regulation of intraocular pressure, neuroimmunomodulation, regulation of arterial blood pressure and in metabolic disorders.

In this article we summarize the current knowledge concerning the GPR18 receptor – its expression, ligands and the in the physiological processes and the pathophysiological conditions.”

https://pubmed.ncbi.nlm.nih.gov/35792647/

https://postepybiochemii.ptbioch.edu.pl/index.php/PB/article/view/399

A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History

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“Background: An oral route of administration for tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ9-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. 

Materials and Methods: Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ9-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ9-THC, 9.76 mg CBD) or MCT (10.0 mg Δ9-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. 

Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ9-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). 

Conclusion: This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant’s cannabis use history, including their age of first use and number of years using cannabis significantly impacted pharmacokinetic parameters investigated. Acute consumption of both products was found to be safe and well tolerated. The results suggest that Solutech may optimize bioavailability from cannabis formulations.”

https://pubmed.ncbi.nlm.nih.gov/35787693/

https://www.liebertpub.com/doi/10.1089/can.2021.0176

Biosynthetic origins of unusual cannabimimetic phytocannabinoids in Cannabis sativa L: A review

Phytochemistry

“Plants of Cannabis sativa L. (Cannabaceae) produce an array of more than 160 isoprenylated resorcinyl polyketides, commonly referred to as phytocannabinoids. These compounds represent molecules of therapeutic importance due to their modulation of the human endocannabinoid system (ECS).

While understanding of the biosynthesis of the major phytocannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has grown rapidly in recent years, the biosynthetic origin and genetic regulation of many potentially therapeutically relevant minor phytocannabinoids remains unknown, which limits the development of chemotypically elite varieties of C. sativa.

This review provides an up-to-date inventory of unusual phytocannabinoids which exhibit cannabimimetic-like activities and proposes putative metabolic origins. Metabolic branch points exploitable for combinatorial biosynthesis and engineering of phytocannabinoids with augmented therapeutic activities are also described, as is the role of phytocannabinoid remodelling to accelerate therapeutic portfolio expansion in C. sativa.”

https://pubmed.ncbi.nlm.nih.gov/35718133/

https://www.sciencedirect.com/science/article/abs/pii/S0031942222001984?via%3Dihub

Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities

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Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate and choline at the neuromuscular junction. Abnormal hyperactivity of AChE and BChE can lead to cholinergic deficiency, which is associated with several neurological disorders including cognitive decline and memory impairments.

Preclinical studies support that some cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC) may exert pharmacological effects on the cholinergic system, but it remains unclear whether cannabinoids can inhibit AChE and BChE activities.

Herein, we aimed to evaluate the inhibitory effects of a panel of cannabinoids including CBD, Δ8-THC, cannabigerol (CBG), cannabigerolic acid (CBGA), cannabicitran (CBT), cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) on AChE and BChE activities.

Results: Cannabinoids including CBD, Δ8-THC, CBG, CBGA, CBT, CBDV, CBC, and CBN (at 200 µM) inhibited the activities of AChE and BChE by 70.8, 83.7, 92.9, 76.7, 66.0, 79.3, 13.7, and 30.5%, and by 86.8, 80.8, 93.2, 87.1, 77.0, 78.5, 27.9, and 22.0%, respectively. The inhibitory effects of these cannabinoids (with IC50 values ranging from 85.2 to >200 µM for AChE and 107.1 to >200 µM for BChE) were less potent as compared to the positive control galantamine (IC50 1.21 and 6.86 µM for AChE and BChE, respectively). In addition, CBD, as a representative cannabinoid, displayed a competitive type of inhibition on both AChE and BChE. Data from the molecular docking studies suggested that cannabinoids interacted with several amino acid residues on the enzyme proteins, which supported their overall inhibitory effects on AChE and BChE.

Conclusion: Cannabinoids showed moderate inhibitory effects on the activities of AChE and BChE enzymes, which may contribute to their modulatory effects on the cholinergic system. Further studies using cell-based and in vivo models are warranted to evaluate whether cannabinoids’ neuroprotective effects are associated with their anti-cholinesterase activities.”

https://pubmed.ncbi.nlm.nih.gov/35702400/

“Previously published work from our group has shown that medicinal plants and their derived natural products show neuroprotective and anti-inflammatory properties.

Notably, cannabinoids from Cannabis sativa (C. sativa) have been increasingly evaluated in studies to treat chronic pain, inflammation, multiple sclerosis, post-traumatic stress disorder, and neurological diseases, specifically AD.

Furthermore, a study implicated that phytochemicals of C. sativa, including several cannabinoids, are inhibitors of AChE,

In summary, several cannabinoids exhibited moderate inhibitory effects against the activities of cholinesterases including AChE and BChE.”

https://www.karger.com/Article/FullText/524086

“Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer’s Disease Therapy”

https://www.frontiersin.org/articles/10.3389/fphar.2018.01192/full


Cannabis decriminalization and racial disparity in arrests for cannabis possession

Social Science & Medicine

“Rationale: Minorities often bear the brunt of unequal enforcement of drug laws. In the U.S., Blacks have been disproportionately more likely to be arrested for cannabis possession than Whites despite a similar rate of cannabis use. Decriminalizing cannabis has been argued as a way to reduce racial disparity in cannabis possession arrests. To date, however, the empirical evidence to support this argument is almost non-existent.

Objectives: To examine whether cannabis decriminalization was associated with reduced racial disparity in arrests for cannabis possession between Blacks and Whites in the U.S.

Methods: Using FBI Uniform Crime Report data from 37 U.S. states, cannabis possession arrest rates were calculated separately for Blacks and Whites from 2000 to 2019. A difference-in-differences framework was used to estimate the association between cannabis decriminalization and racial disparity in cannabis possession arrest rates (Blacks/Whites ratio) among adults and youths.

Results: Cannabis possession arrest rates declined over 70% among adults and over 40% among youths after the implementation of cannabis decriminalization in 11 states. Among adults, decriminalization was associated with a roughly 17% decrease in racial disparity in arrest rates between Blacks and Whites. Among youths, arrest rates declined among both Blacks and Whites but there was no evidence for a change in racial disparity between Blacks and Whites following decriminalization.

Conclusions: Cannabis decriminalization was associated with substantially lower cannabis possession arrest rates among both adults and youths and among both Blacks and Whites. It reduced racial disparity between Blacks and Whites among adults but not youths. These findings suggested that cannabis decriminalization had its intended consequence of reducing arrests and may have potential to reduce racial disparity in arrests at least among adults.”

https://pubmed.ncbi.nlm.nih.gov/34954673/

“Cannabis decriminalization decreased arrests in both adults and youths.•

Cannabis decriminalization decreased arrests in both Blacks and Whites.•

Cannabis decriminalization decreased racial disparity in arrests only in adults.”

https://www.sciencedirect.com/science/article/abs/pii/S0277953621010042?via%3Dihub

“Cannabis Decriminalization Reduces The Racial Disparity, A New Study Suggests”

https://www.forbes.com/sites/dariosabaghi/2021/12/28/cannabis-decriminalization-reduces-the-racial-disparity-a-new-study-suggests/?sh=305b32d91357


Medical cannabis and automobile accidents: Evidence from auto insurance

“While many states have legalized medical cannabis, many unintended consequences remain under-studied. We focus on one potential detriment-the effect of cannabis legalization on automobile safety. We examine this relationship through auto insurance premiums.

Employing a modern difference-in-differences framework and zip code-level premium data from 2014 to 2019, we find that premiums declined, on average, by $22 per year following medical cannabis legalization. The effect is more substantial in areas near a dispensary and in areas with a higher prevalence of drunk driving before legalization.

We estimate that existing legalization has reduced health expenditures related to auto accidents by almost $820 million per year with the potential for a further $350 million reduction if legalized nationally.”

https://pubmed.ncbi.nlm.nih.gov/35691014/

https://onlinelibrary.wiley.com/doi/10.1002/hec.4553