The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.

Beyond THC and Endocannabinoids.

Research in the cannabinoid field, namely on phytocannabinoids, the endogenous cannabinoids anandamide and 2-arachidonoyl glycerol and their metabolizing and synthetic enzymes, the cannabinoid receptors, and anandamide-like cannabinoid compounds, has expanded tremendously over the last few years. Numerous endocannabinoid-like compounds have been discovered. The Cannabis plant constituent cannabidiol (CBD) was found to exert beneficial effects in many preclinical disease models ranging from epilepsy, cardiovascular disease, inflammation, and autoimmunity to neurodegenerative and kidney diseases and cancer. CBD was recently approved in the United States for the treatment of rare forms of childhood epilepsy. This has triggered the development of many CBD-based products for human use, often with overstated claims regarding their therapeutic effects. In this article, the recently published research on the chemistry and biological effects of plant cannabinoids (specifically CBD), endocannabinoids, certain long-chain fatty acid amides, and the variety of relevant receptors is critically reviewed.

Queen fecundity, worker entourage and cuticular chemistry in the ant Formica fusca.

Cooperative breeding entails conflicts over reproductive shares that may be settled in different ways. In ants, where several queens simultaneously reproduce in a colony, both queens and workers may influence the reproductive apportionment and offspring quality. Queens may vary in their intrinsic fecundity, which may influence the size of the worker entourage attending individual queens, and this may eventually dictate the reproductive output of a queen. We tested whether the reproductive success of queens is affected by the size of their worker entourage, their fecundity at the onset of the reproductive season, and whether the queen cuticular hydrocarbon profile carries information on fecundity. We show that in the ant Formica fusca both queen fecundity and egg hatching success increase with the size of their entourage, and that newly hatched larvae produced by initially highly fecund queens are smaller. Furthermore, higher relatedness among workers increased queen fecundity. Finally, the queens that received a large worker entourage differed in the cuticular chemistry from those that received a small worker entourage. Our results thus show that workers play a pivotal role in determining queen fitness, that high intracolony relatedness among workers enhances the overall reproductive output in the colony, and that queen fecundity is reflected in their cuticular hydrocarbon profile.

Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis.

Cannabis-based terpenes are believed to modulate physiological responses to disease and alter the efficacy of cannabinoids in the so-called "entourage effect". The monoterpene myrcene can reduce nociception produced by noxious thermal and mechanical stimuli as well as reducing acute inflammation. The current study examined the role of myrcene and cannabidiol (CBD) in controlling chronic joint inflammation and pain. Chronic arthritis was induced in male Wistar rats by intra-articular injection of Freund's complete adjuvant into the right knee. On days 7 and 21 after arthritis induction, joint pain (von Frey hair algesiometry), inflammation (intravital microscopy, laser speckle contrast analysis) and joint histopathology were assessed. Local application of myrcene (1 and 5 mg/kg s.c.) reduced joint pain and inflammation via a cannabinoid receptor mechanism. The combination of myrcene and CBD (200 µg) was not significantly different from myrcene alone. Repeated myrcene treatment had no effect on joint damage or inflammatory cytokine production. These data suggest that topical myrcene has the potential to reduce chronic arthritis pain and inflammation; however, it has no synergistic effect with CBD.

Acetone as Artifact of Analysis in Terpene Samples by HS-GC/MS.

Cannabis-infused product manufacturers often add terpenes to enhance flavor. Meanwhile, labeling requirements for these same products necessitate testing for residual solvent levels. We have found that heating terpene samples containing an oxygen or air atmosphere results in the detection of significantly higher levels of acetone when compared to the same compound in argon atmosphere using temperature regimes common to headspace autosampler routines. This formation was statistically significant (p = 0.05) for most of the predominant terpenes found in cannabis. The largest increase in acetone formation was seen for terpinolene which showed an 885% increase in oxygen atmosphere (4603.6 PPM) when compared to analysis under argon (519.9 PPM). Cannabinoids were shown to reduce this formation and explain why high levels of acetone are not reported in cannabis extracts, even though these can contain up to 40% terpenes.

Optimal Treatment with Cannabis Extracts Formulations Is Gained via Knowledge of Their Terpene Content and via Enrichment with Specifically Selected Monoterpenes and Monoterpenoids.

Differences between therapeutic effects of medical cannabis inflorescences and those of their extracts are generally attributed to the differences in administration form and in the resultant pharmacokinetics. We hypothesized that difference may further extend to the composition of the actually consumed drug. Cannabinoid and terpene contents were compared between commercial cannabis inflorescences (n = 19) and decarboxylated extracts (n = 12), and between inflorescences and decarboxylated extracts produced from them (n = 10). While cannabinoid content was preserved in the extracts, a significant loss of terpenes was evident, mainly in the more volatile monoterpenes and monoterpenoids (representing a loss of about 90%). This loss changes the total terpene content, the proportion of monoterpenes out of the total terpenes, and the monoterpene/cannabinoid ratio. Terpene deficiency might impair extracts' pharmacological efficacy and might contribute to the patients' preference to inflorescences-smoking. This argues against the validity of terms such as "whole plant" and "full spectrum" extracts and creates a misleading assumption that extracts represent the pharmacological profile of the sourced inflorescences. Furthermore, it reduces the diversity in extracts, such as loss of differences between sativa-type and indica-type. Enriching cannabis extracts with selected terpenes may provide a suitable solution, generating a safe, precise, and reproducible drug with tailored cannabinoid and terpene contents. Careful selection of terpenes to be added enables tailor-made extracts, adjusted for various medicinal aims and for different populations.

Parents about parenting dual career athletes: A systematic literature review.

OBJECTIVES: To establish the scientific literature on the parents' view as supporters of dual career (DC) athletes, and to highlight practical implications for the development of education programmes to empower parents in this role. METHOD: ology: The systematic literature review included four electronic databases, from which 438 articles published in English between 1999 and 2019 were retrieved. RESULTS: A total of 14 studies achieved the eligibility criteria (i.e., focus on DC, involving parents as participants) for inclusion. Results show that the 14 studies included in the review were characterised by sample sizes <15 to >50 parents of individual and/or team sports athletes, involving data collection based on interviews, semi-structured interviews focus groups, questionnaires and a survey. A thematic synthesis highlighted a two primary constructs: the individual level and the inter-individual level, respectively. The individual level comprised two main themes: Approach to both Sport and Education, and Stressors and Coping, which included five aspects of parenting. The inter-individual level presented three themes: Relationship with the Athlete; Relationship with the Sport Environment and Relationship with the Academic Environment. CONCLUSIONS: Findings highlighted a relevant parental role in supporting DC athletes and partial information on parental support strategies. In conclusions, the limited sample size and typology of sports, and the partial representativeness of countries have impacted the global application of the main findings. Furthermore, the need of an educational programme for parents and the need of regular parents-athlete-teacher/coach engagement were considered crucial to facilitate successful parental interventions at academic and/or sports levels and to limit the potential negative effects of DC parenting.

Role of Caryophyllane Sesquiterpenes in the Entourage Effect of Felina 32 Hemp Inflorescence Phytocomplex in Triple Negative MDA-MB-468 Breast Cancer Cells.

Cannabis sativa L. crops have been traditionally exploited as sources of fibers, nutrients, and bioactive phytochemicals of medical interest. In the present study, two terpene-rich organic extracts, namely FOJ and FOS, obtained from Felina 32 hemp inflorescences collected in June and September, respectively, have been studied for their in vitro anticancer properties. Particularly, their cytotoxicity was evaluated in different cancer cell lines, and the possible entourage effect between nonintoxicating phytocannabinoids (cannabidiol and cannabichromene) and caryophyllane sesquiterpenes (ß-caryophyllene, ß-caryophyllene oxide and α-humulene), as identified at GC/MS analysis, was characterized. Modulation of cannabinoid CB1 and CB2 receptors was studied as a mechanistic hypothesis. Results highlighted marked cytotoxic effects of FOJ, FOS, and pure compounds in triple negative breast cancer MDA-MB-468 cells, likely mediated by a CB2 receptor activation. Cannabidiol was the main cytotoxic constituent, although low levels of caryophyllane sesquiterpenes and cannabichromene induced potentiating effects; the presence in the extracts of unknown antagonistic compounds has been highlighted too. These results suggest an interest in Felina 32 hemp inflorescences as a source of bioactive phytocomplexes with anticancer properties and strengthen the importance of considering the possible involvement of minor terpenes, such as caryophyllane sesquiterpenes, in the entourage effect of hemp-based extracts.

[Memory(ies) at risk ]. / Mémoire(s) en péril.

When an elderly person suffers from severe memory problems, it is useful to look at the behaviour of those around him or her. Serious "absences" can be observed, revealing an intergenerational memory at risk.

[Caregiver burden: From recognition to care]. / Le fardeau des aidants : de la reconnaissance à la prise en charge.

The burden of caregivers of patients with chronic diseases has been the subject of research for several years, but few studies have focused on the suffering of family members from the time of their first hospitalization in psychiatry. The identification of the determinants of this burden would allow us to propose early management aimed at improving the well-being of the patients' family and friends and maximizing intra-family resources.

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity.

Mixtures of different Cannabis sativa phytocannabinoids are more active biologically than single phytocannabinoids. However, cannabis terpenoids as potential instigators of phytocannabinoid activity have not yet been explored in detail. Terpenoid groups were statistically co-related to certain cannabis strains rich in Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA), and their ability to enhance the activity of decarboxylase phytocannabinoids (i.e., THC or CBD) was determined. Analytical HPLC and GC/MS were used to identify and quantify the secondary metabolites in 17 strains of C. sativa, and correlations between cannabinoids and terpenoids in each strain were determined. Column separation was used to separate and collect the compounds, and cell viability assay was used to assess biological activity. We found that in "high THC" or "high CBD" strains, phytocannabinoids are produced alongside certain sets of terpenoids. Only co-related terpenoids enhanced the cytotoxic activity of phytocannabinoids on MDA-MB-231 and HCT-116 cell lines. This was found to be most effective in natural ratios found in extracts of cannabis inflorescence. The correlation in a particular strain between THCA or CBDA and a certain set of terpenoids, and the partial specificity in interaction may have influenced the cultivation of cannabis and may have implications for therapeutic treatments.

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

BACKGROUND: Cannabis-based drugs have been shown to be effective in inflammatory diseases. A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoid receptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues. These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed "entourage" compounds due to their ability to modulate the endocannabinoid system. The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well. RESULTS: AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints. CONCLUSION: The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.

Where's my entourage? The curious case of 2-oleoylglycerol, 2-linolenoylglycerol, and 2-palmitoylglycerol.

2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid in the brain and an agonist at two cannabinoid receptors (CB1 and CB2). The synthesis, degradation and signaling of 2-AG have been investigated in detail but its relationship to other endogenous monoacylglycerols has not been fully explored. Three congeners that have been isolated from the CNS are 2-linoleoylglycerol (2-LG), 2-oleoylglycerol (2-OG), and 2-palmitoylglycerol (2-PG). These lipids do not orthosterically bind to cannabinoid receptors but are reported to potentiate the activity of 2-AG, possibly through inhibition of 2-AG degradation. This phenomenon has been dubbed the 'entourage effect' and has been proposed to regulate synaptic activity of 2-AG. To clarify the activity of these congeners of 2-AG we tested them in neuronal and cell-based signaling assays. The signaling profile for these compounds is inconsistent with an entourage effect. None of the compounds inhibited neurotransmission via CB1 in autaptic neurons. Interestingly, each failed to potentiate 2-AG-mediated depolarization-induced suppression of excitation (DSE), behaving instead as antagonists. Examining other signaling pathways we found that 2-OG interferes with agonist-induced CB1 internalization while 2-PG modestly internalizes CB1 receptors. However in tests of pERK, cAMP and arrestin recruitment, none of the acylglycerols altered CB1 signaling. Our results suggest 1) that these compounds do not serve as entourage compounds under the conditions examined, and 2) that they may instead serve as functional antagonists. Our results suggest that the relationship between 2-AG and its congeners is more nuanced than previously appreciated.

[Excessive alcohol consumption: what is the burden on natural caregivers?]. / La consommation excessive d'alcool: un lourd fardeau pour l'entourage.

BACKGROUND: Data on the natural caregivers burdened by the excessive consumption of alcohol by members of the family circle or friends in the general population are lacking. Therefore, our aim was twofold: (i) to assess the burden of individuals with excessive alcohol consumption on natural caregivers and (ii) to examine the factors explaining the association between alcohol consumption and the level of burden. METHOD: Data were derived from a national representative survey of the French adult population, conducted in 2013, that involved 1018 participants who had in their close environment a person consuming excessive amounts of alcohol. The level of burden was assessed using the Zarit Burden Scale (ZBI). RESULTS: The average score of the ZBI was 28.5 (SE=16.0). The average volume of alcohol consumed per day, heavy drinking days, as well as the consumers' profiles defined by the AUDIT-C were significantly associated with the level of burden. Following adjustments for the participants' characteristics and for the closeness between participants and individuals with excessive consumption, these associations remained significant. Following adjustments for these variables as well as demographic, social, behavioral and medical characteristics of individuals with excessive consumption, the associations between the level of burden and respectively consumers' profiles and heavy drinking days remained significant. At last, following adjustments for social, behavioral and medical characteristics of individuals with excessive consumption and for the closeness between them and participants, only the association between heavy drinking days and the level of burden remained significant. CONCLUSIONS: One out of five participants having in their close environment a person consuming excessive amount of alcohol reported an important burden. The association between the individuals' alcohol intake and the level of burden for natural caregivers was mainly influenced by social, behavioral and medical consequences of alcohol consumption and by the physical and affective proximity between them. Furthermore, we found that the AUDIT-C scores could define alcohol consumers' profiles which form a continuum in terms of the level of burden, even after adjustments for potentially confounding variables. At last, the high prevalence of psychological complications in participants calls for greater recognition of the natural caregivers' burden in the management of patients with alcohol dependence.

Dual career through the eyes of university student-athletes in the Republic of Kosovo.

Introduction: The successful combination of a sports career and education, known as the dual career, requires cooperation and a multi-dimensional approach. Although extensive research has been conducted on dual career programs and services in developed countries, there is limited information available on the dual-career phenomenon in developing countries. This study aimed to explore the dual career experiences of university student-athletes in the Republic of Kosovo. Materials and methods: A 30-item online survey was distributed to student-athletes, addressing various aspects of the dual career. A total of 121 student-athletes (males: 63.6%; females: 36.4%) voluntarily participated in the survey. Results: These student-athletes represented 13 different sports, with 102 (84.3%) participating in team and 19 (15.7%) in individual sports. Between individual and team sports no significant differences were found regarding university and sports engagement, and the time required to travel from the university to the training venue, whereas a significant difference (p = 0.019) emerged for the time needed to travel from home to the training venue. Significant differences (p < 0.05) were found between university majors in terms of sports engagement. The present findings highlight a lack of familiarity with dual career programs among student-athletes (89.3%) and the need for dual-career policies at the university (16.5%), sport (9.9%), and national (13.2%) levels. Student-athletes faced various challenges, mainly related to limited leisure time (62.8%), academic overload (60.3%), frequent absence from classes (59.6%), and financial uncertainty (35.5%). Recommended improvements included increased financial support (66.1%), the availability of sports facilities at or near the university (48.8%), greater educational flexibility (26.4%), tutoring services at the university (25.6%), and sports clubs (19%) levels, as well as improved communication regarding existing initiatives and legal aspects (53.7% and 47.1%, respectively). The study also identified parents (98.3%), coaches (86%), and siblings (60.3%) as important sources of support for student-athletes at personal, sports, and university levels. Conclusions: In conclusion, to enhance the potential of future student-athletes in the Republic of Kosovo, relevant stakeholders in sports and higher education should collaborate closely and implement programs and services based on international best practices for dual-career support.

In Vitro and In Vivo Anti-Inflammatory and Antidepressant-like Effects of Cannabis sativa L. Extracts.

Cannabis sativa L. has been widely used by humans for centuries for various purposes, such as industrial, ceremonial, medicinal, and food. The bioactive components of Cannabis sativa L. can be classified into two main groups: cannabinoids and terpenes. These bioactive components of Cannabis sativa L. leaf and inflorescence extracts were analyzed. Mice were systemically administered 30 mg/kg of Cannabis sativa L. leaf extract 1 h before lipopolysaccharide (LPS) administration, and behavioral tests were performed. We conducted an investigation into the oxygen saturation, oxygen tension, and degranulation of mast cells (MCs) in the deep cervical lymph nodes (DCLNs). To evaluate the anti-inflammatory effect of Cannabis sativa L. extracts in BV2 microglial cells, we assessed nitrite production and the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. The main bioactive components of the Cannabis sativa L. extracts were THCA (a cannabinoid) and ß-caryophyllene (a terpene). Cannabis sativa L. leaf extract reduced the immobility time in the forced swimming test and increased sucrose preference in the LPS model, without affecting the total distance and time in the center in the open field test. Additionally, Cannabis sativa L. leaf extract improved oxygen levels and inhibited the degranulation of MCs in DCLNs. The Cannabis sativa L. extracts inhibited IL-1ß, IL-6, TNF-α, nitrite, iNOS, and COX-2 expression in BV2 microglia cells. The efficacy of Cannabis sativa L. extracts was suggested to be due to the entourage effect of various bioactive phytochemicals. Our findings indicate that these extracts have the potential to be used as effective treatments for a variety of diseases associated with acute inflammatory responses.

[Social connection: a report of the SFGM-TC on the maintaining social and family connections during Hematopoietic Stem Cell Transplantation]. / Lien social: maintien du lien social et familial pendant l'allogreffe de CSH.

OBJECTIVE: To set up the minimal conditions necessary to ensure that the social and familial network of the patient is preserved during the hospital stay for allogeneic hematopoïetic stem cell transplantation. MATERIAL AND METHODS: A national survey was conducted to increase knowledge about the conditions of hospital stay of adult and pediatric stem cell recipients. Then a multidisciplinary panel of health workers including doctors and nurses met to establish recommendations for maintaining the social and familial relationships optimally during the HSCT procedure. RESULTS: Practices and policies are very heterogeneous among the transplant centers. No consensus has been established and the literature data are scarce. The panel has thus established a list of recommendations to maintain optimal relationships between the patient and his relatives and friends during the hospital stay. The objective is to ensure a better acceptation of the isolation conditions and to facilitate the return home after D30. CONCLUSION: Since there is no established scientific background for drastic isolation conditions, a multi-disciplinary approach in relationship with patients associations should allow softening of the procedures without impairing the quality of care.

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers.

This study investigates the potential of cannabidiol (CBD), one major cannabinoid of the plant Cannabis sativa, alone and in combination with a terpene-enriched extract from Humulus lupulus ("Hops 1"), on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation. With the present study, we could support earlier findings of the anti-inflammatory potential of CBD, which showed a dose-dependent [0-5 µM] reduction in nitric oxide and tumor necrosis factor-alpha (TNF-α) released by LPS-stimulated RAW 264.7 macrophages. Moreover, we observed an additive anti-inflammatory effect after combined CBD [5 µM] and hops extract [40 µg/mL] treatment. The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single substance treatments and akin to the control hydrocortisone. Furthermore, cellular CBD uptake increased dose-dependently in the presence of terpenes from Hops 1 extract. The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration, as indicated by comparison with a hemp extract containing both CBD and terpenes. These findings may contribute to the postulations for the so-called "entourage effect" between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabinoid source, such as hops, for the treatment of inflammatory diseases.

Systematic combinations of major cannabinoid and terpene contents in Cannabis flower and patient outcomes: a proof-of-concept assessment of the Vigil Index of Cannabis Chemovars.

BACKGROUND: Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects. METHODS: Between 09/10/2016 and 03/11/2021, 204 people used the freely available, educational mobile software application, Releaf App, to record 6309 real-time consumption sessions using 633 distinct Cannabis flower products, unique at the user level, with terpene and cannabinoid potency information. The indexing system is based on retrospective data analysis of the products' primary and secondary terpene contents and tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies and yielded a total of 478 distinct chemovars. Analyses of covariances (ANCOVAs) were used to compare symptom levels and side effects experienced across the five most common chemovars before and after cannabis consumption for app users overall and for those treating chronic pain and depression or anxiety. RESULTS: Examination of the five most frequently consumed chemovars showed significant differences in symptom treatment effectiveness for chronic pain and for depression and anxiety (ps < .001). While the effects varied in magnitude, the five chemovars were effective across conditions except for MC61 (mercene .01-0.49%/beta-caryophyllene .01 to 0.49%/THC 20-25%/CBD 0.01-1.0%), which exacerbated feelings of anxiety or depression. The chemovars also differed in their association with experiencing positive, negative, and context-specific side effects, with two chemovars, MC61 and MC62 (mercene .01-0.49%/beta-caryophyllene .01-0.49%/THC 20-25%/CBD 1-5%), generating two to three fewer positive side effects and as much as one more negative and two more context-specific side effects than the other three chemovars. CONCLUSIONS: The findings provide "proof-of-concept" that a simple, yet comprehensive chemovar indexing system can be used to identify systematic differences in clinically relevant patient health outcomes and other common experiences across Cannabis flower products, irrespective of the product's commercial or strain name. This study was limited by self-selection into cannabis and app use and a lack of user-specific information. Further research using this chemovar indexing system should assess how distinct combinations of phytochemicals interact with user-level characteristics to produce general and individualized Cannabis consumption experiences and health outcomes, ideally using randomized methods to assess differences in effects across chemovars.

The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model.

In the present study, cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and combinations of CBD and THC, were evaluated in the mouse maximal electroshock (MES) seizure test - an animal model of generalized-onset seizures. Male CF-1 mice were injected intraperitoneally (i.p.) with either CBD, THC or a combination of CBD and THC. The MES test was conducted 2 h after the injection of CBD and 1 h after the injection of THC. A wide range of doses was tested to allow the construction of dose-response curves. Toxicity was assessed using a behavioral rating scale. It was found that: 1) the ED50 for THC alone was 52 mg/kg and its therapeutic index (TI) was 1.7; 2) the ED50 for CBD alone was 190 mg/kg and its TI was 2.4; and 3) the ED50 for a 15:1 combination of CBD+THC was 130 mg/kg + 8.6 mg/kg (CBD + THC). Thus, CBD and THC were both effective in the MES model, and CBD was somewhat more effective in the presence of low (non-therapeutic) doses of THC. The improvement in CBD's effect, however, was less dramatic than that seen in past experiments with the amygdala-kindling model (Fallah et al., 2021). Both CBD alone and CBD+THC in combination might be useful in the treatment of generalized-onset seizures. The advantage of adding THC to CBD, however, might be less than in the treatment of focal-onset seizures.