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

Investigating the Effects of a Synthetic Cannabinoid on the Pathogenesis of Leukemia and Leukemic Stem Cells: A New Therapeutic Approach

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“The popularity and usage of synthetic cannabinoids (SCs) are increasing due to their easy accessibility and psychoactive effects worldwide. Studies on cannabinoids on leukemic stem cells (LSC) and hematopoietic stem cells (HSCs), which are the precursors of leukemia cells, generally depend on the natural cannabinoid delta-9-THC. As there is only a limited number of studies focusing on the results of SC applications, the reflections upon LSCs have to be clarified.

In this study, biological responses and antileukemic effects of JWH-018-one of the first produced and widely used SCs-were evaluated upon leukemia cells. Whether JWH-018 exhibited a preventive effect on both leukemic and HSCs was evaluated by presenting a therapeutic approach for the first time in the literature. Cells were analyzed in case of cell proliferation, apoptosis, and transcriptional expression profiling of some significant JAK/STAT and AKT/mTOR pathways, apoptotic, cell cycle regulation, and epigenetic chromatin remodeling-related genes following JWH-018 treatment.

In conclusion, however, further studies are still needed upon both HSCs and LSCs to illuminate the effects of SCs on leukemogenesis on chronic myeloid leukemia (CML) more clearly; we consider that the JWH-018 can provide a therapeutic effect on the pathogenesis of leukemia and particularly upon LSCs and SCs might have therapeutic potential in addition to current therapy.”

https://pubmed.ncbi.nlm.nih.gov/35834597/

https://www.liebertpub.com/doi/10.1089/can.2021.0180

“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns. Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.”

https://pubmed.ncbi.nlm.nih.gov/26775260/

“Cannabinoid CP55940 selectively induces apoptosis in Jurkat cells and in ex vivo T-cell acute lymphoblastic leukemia through H 2 O 2 signaling mechanism. Our findings support the use of cannabinoids as a potential treatment for T-ALL cells.”

https://pubmed.ncbi.nlm.nih.gov/32540572/

“CP 55,940 is a synthetic cannabinoid which mimics the effects of naturally occurring THC (one of the psychoactive compounds found in cannabis)”  https://en.wikipedia.org/wiki/CP_55,940

“Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Plant-derived cannabinoids, including Delta9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells”

https://pubmed.ncbi.nlm.nih.gov/16908594/


Impact of the cannabinoid system in Alzheimer’s diseases

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“Cannabinoids are compounds that were initially isolated from cannabis marihuana and are also widely present in both nervous and immune systems of animals.

In recent years, with in-depth research on cannabinoids, their clinical medicinal value has been evaluated, and many exciting achievements have been continuously accumulating, especially in the field of neurodegenerative disease.

Alzheimer’s disease is the most common type of neurodegenerative disease that causes dementia and has become a global health problem that seriously impacts human health today.

In this review, we discuss the therapeutic potential of cannabinoids for the treatment of Alzheimer’s disease.

How cannabinoids act on different endocannabinoid receptor subtypes to regulate Alzheimer’s disease, the roles of the endocannabinoid system in Alzheimer’s disease are outlined, and the underlying mechanisms are discussed.

Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to Alzheimer’s disease and discuss the potential usefulness of cannabinoids in the clinical treatment of Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/35105293/

https://www.eurekaselect.com/article/120593

The Memory Benefit to Aged APP/PS1 Mice from Long-Term Intranasal Treatment of Low-Dose THC

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“THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery.

Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group.

An enzyme-linked immunosorbent assay showed that the Aβ1-40 and 1-42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment.

Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer’s disease-related cognitive performance.”

https://pubmed.ncbi.nlm.nih.gov/35457070/

https://www.mdpi.com/1422-0067/23/8/4253

“Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice.  In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.”

https://pubmed.ncbi.nlm.nih.gov/35269905/

Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report

ISRCTN - Publish with BioMed Central

“Background: Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer’s disease, and cannabinoid-based therapy appears to be a feasible possibility.

Case presentation: This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer’s disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-Cognitive Subscale were performed.

Conclusions: Here we provide original evidence that cannabinoid microdosing could be effective as an Alzheimer’s disease treatment while preventing major side effects. This is an important step toward dissociating cannabinoids’ health-improving effects from potential narcotic-related limitations.”

https://pubmed.ncbi.nlm.nih.gov/35820856/

“In summary, data presented in this case report suggest that cannabinoid microdosing is a potential therapeutic for AD, with no significant side effects, although placebo-controlled clinical trials are needed to confirm and extend these data.”

https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-022-03457-w

The Combination of Δ 9-Tetrahydrocannabinol and Cannabidiol Suppresses Mitochondrial Respiration of Human Glioblastoma Cells via Downregulation of Specific Respiratory Chain Proteins

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“Phytocannabinoids represent a promising approach in glioblastoma therapy.

Previous work has shown that a combined treatment of glioblastoma cells with submaximal effective concentrations of psychoactive Δ9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD) greatly increases cell death.

In the present work, the glioblastoma cell lines U251MG and U138MG were used to investigate whether the combination of THC and CBD in a 1:1 ratio is associated with a disruption of cellular energy metabolism, and whether this is caused by affecting mitochondrial respiration.

Here, the combined administration of THC and CBD (2.5 µM each) led to an inhibition of oxygen consumption rate and energy metabolism. These effects were accompanied by morphological changes to the mitochondria, a release of mitochondrial cytochrome c into the cytosol and a marked reduction in subunits of electron transport chain complexes I (NDUFA9, NDUFB8) and IV (COX2, COX4). Experiments with receptor antagonists and inhibitors showed that the degradation of NDUFA9 occurred independently of the activation of the cannabinoid receptors CB1, CB2 and TRPV1 and of usual degradation processes mediated via autophagy or the proteasomal system.

In summary, the results describe a previously unknown mitochondria-targeting mechanism behind the toxic effect of THC and CBD on glioblastoma cells that should be considered in future cancer therapy, especially in combination strategies with other chemotherapeutics.”

https://pubmed.ncbi.nlm.nih.gov/35804909/

“Cannabidiol (CBD) is a phytocannabinoid from Cannabis sativa L. that exhibits no psychoactivity and, like the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), shows anticancer effects in preclinical cell and animal models. Previous studies have indicated a stronger cancer-targeting effect when THC and CBD are combined. Here, we investigated how the combination of THC and CBD in a 1:1 ratio affects glioblastoma cell survival. The compounds were found to synergistically enhance cell death, which was attributed to mitochondrial damage and disruption of energy metabolism. A detailed look at the mitochondrial electron transfer chain showed that THC/CBD selectively decreased certain subunits of complexes I and IV. These data highlight the fundamental changes in cellular energy metabolism when cancer cells are exposed to a mixture of cannabinoids and underscore the potential of combining cannabinoids in cancer treatment.”

https://www.mdpi.com/2072-6694/14/13/3129


Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation

“The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis.

Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management.

Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors.

In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment.

This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/35796303/

“Cannabis sativa L. is a natural source of valuable compounds that comprise cannabinoid agonists and antagonists, which have recently been scanned for future applications as anti-tumor drugs. Cannabinoids have mostly been used as a part of palliative care to alleviate pain, relieve nausea, and stimulate appetite in cancer patients. Although not yet approved for treating tumor progression, cannabinoid agonist/antagonists on the tumor microenvironment have been studied for the last 43 years. Research on cannabinoids and their potential therapeutic function has been ongoing since 1971. Numerous in vitro and in vivo studies have demonstrated the anti-cancer effects of cannabinoids in various cancer types.”

https://journals.sagepub.com/doi/10.1177/15347354221096766


Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

SpringerLink

“Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells.

The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain.

THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.”

https://pubmed.ncbi.nlm.nih.gov/35796920/

“Tetrahydrocannabinol (THC) and cannabidiol (CBD) combination medicines and CBD-only medicines are prospective new treatments for chronic pain, stress, anxiety, depression, and insomnia, which are all medical conditions in need of better therapeutics. Both THC/CBD combination and CBD-only medicines could provide effective new treatment options for pain and mental health, respectively, and both have good safety and tolerability profiles relative to the current treatments.

THC and CBD combination medicines have a good safety and tolerability profile that is appropriate for opioid stage (stage 2–3) treatment of chronic pain. Low-dose CBD could be used as an initial treatment for chronic pain and for stress, anxiety, depression, and insomnia. High quality efficacy evidence is best for THC/CBD combination medicines for chronic pain and CBD-only medicines for stress and anxiety. “

https://link.springer.com/article/10.1007/s10787-022-01020-z

Patient Experience and Perspective on Medical Cannabis as an Alternative for Musculoskeletal Pain Management

JAAOS - Journal of the American Academy of Orthopaedic Surgeons

“Introduction: The current rate of opioid prescription is disquieting because of their high abuse potential, adverse effects, and thousands of overdose deaths. This situation imposes urgency in seeking alternatives for adequate pain management. From this perspective, this study aimed to evaluate the experience and the perceived analgesic efficacy of medical cannabis in managing the pain associated with musculoskeletal conditions.

Methods: A 28-question survey was distributed to patients at a major medical cannabis center in Puerto Rico for 2 months. Demographics, medical history, cannabis usage, cannabis use perspective, and analgesic efficacy were assessed in the questionnaire.

Results: One hundred eighty-four patients completed our survey. The majority (67%) were males, and the participants’ average age was 38 years. This study showed an average pain reduction score of 4.02 points on the Numeric Rating Scale among all the participants. Those with musculoskeletal conditions reported a notable average pain reduction score of 4.47 points. In addition, 89% of the participants considered medical cannabis to be more effective than narcotics for adequate pain management.

Conclusions: This study demonstrated that the use of medical cannabis among patients with musculoskeletal conditions effectively reduced pain levels based on their Numeric Rating Scale reported scores.”

https://pubmed.ncbi.nlm.nih.gov/35796526/

“This study showed that the use of medical cannabis among patients with musculoskeletal conditions effectively reduced pain levels based on their NRS reported scores. In addition, most patients using medical cannabis considered that this drug represents a better option than narcotics (ie, opioids) for adequate pain management.”

https://journals.lww.com/jaaosglobal/Fulltext/2022/07000/Patient_Experience_and_Perspective_on_Medical.6.aspx

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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