A Pilot Study on Cannabidiol (CBD) and Eccentric Exercise: Impact on Inflammation, Performance, and Pain.

Study objectives: To investigate the effect of differing doses of the combination of acetazolamide and dronabinol (Aceta-Dro) on the obstructive sleep apnea (OSA) endotypes and their relationship to OSA severity. Methods: We retrospectively analysed data from a double-blind, randomized, placebo-controlled trial of 3 different doses of Aceta-Dro [Low (125mg/2.5 mg), Medium (250mg/5 mg), High (500mg/10 mg)] in OSA patients. OSA endotypes (collapsibility [VPASSIVE], Loop gain [LG], Arousal threshold [ArTH], and muscle compensation [VCOMP]) were extracted from polysomnography signals using validated algorithms. Linear mixed models were employed to assess the impact of treatment condition on the endotypes. Linear regressions assessed the relationship between the changes in endotypes vs. apnea-hypopnea index (AHI) and to predict treatment response from baseline endotypes. Results: Relative to placebo, Aceta-Dro dose-dependently reduced LG by 11% (p = 0.18), 18.5% (p = 0.022) and 20.5% (p = 0.016). The reduction in LG was associated with a decrease in AHI in only the high dose condition (R2 = 0.78, p = 0.004). Aceta-Dro improved VPASSIVE in the low dose condition (+13%, p = 0.005) only, which was strongly associated with AHI reduction (R2 = 0.71, p = 0.005). Aceta-Dro had no impact on VCOMP or ArTH. A higher baseline LG predicted treatment response in the high dose (R2 = 0.56, p = 0.03), with a similar trend observed in the low dose group. More severe collapsibility (lower VPASSIVE) predicted treatment response to both low (R2 = 0.46, p = 0.07) and medium dose (R2 = 0.50, p = 0.03) conditions.

Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors

Chronic pain is a pervasive health issue in the United States, affecting up to 50 million adults and contributing to a substantial economic burden. The worsening opioid crisis has increased the need for nonopiate, nonaddictive alternatives to pain management. Cannabidiol (CBD) has recently garnered attention for its potential analgesic and anti-inflammatory properties without addictive or dependence potential. However, there is limited research regarding the efficacy and safety of CBD in the treatment of chronic pain. This study aimed to explore the use of CBD isolate in adults suffering from chronic pain. We decided to investigate its perceived effectiveness, dosage, frequency of use, and reported side effects through a publicly available, completely anonymous Qualtrics survey. This survey was posted online and in multiple medical clinics. The key findings of our anonymous online survey are that the use of cannabinoids is positively associated with decreased chronic pain, even at low dosages (<100 mg). In addition, though some mild side effects are noted, the majority of patients self-report no side effects, and there are no noted severe side effects. These findings suggest that CBD may serve as a promising alternative to conventional pain management strategies. However, the results warrant further investigation and research into the efficacy and safety of CBD for chronic pain. We believe these data point the way for new and continued avenues of research that can better optimize treatment regimens and help patients with chronic pain.

ABSTRACTBackground: Considering the poorly understood etiology and complex symptoms of chronic neuropathic pain (NP), the lack of effective treatments, and sex-dependent differences in the neuroimmune system as well as in antinociceptive responses to existing pharmacological agents, the potential to therapeutically target the endocannabinoid system as a means of treating this type of intractable pain is clinically relevant and timely. Chronic NP may involve the utilization of distinct immune cell populations in males and females that differentially affect supraspinal and spinal neuromodulation. It is therefore important to investigate the effects of cannabidiol (CBD) on chronic NP-induced nociceptive responses in both sexes.Aims: Evaluating whether the expression of markers associated with CD4+ T cells are affected by CBD in a sexually dimorphic manner will provide key insights into the contribution of these adaptive immune cells to the onset and progression of NP.Methods: Future research will be directed toward examining the potential sex-dependent effects of this nonpsychotropic cannabinoid relative to vehicle in a preclinical model of chronic postsurgical NP. Specifically, (1) differences in nociceptive behavior, (2) chronic changes in neural firing patterns, and (3) up- or downregulation of markers associated with CD4+ T cells in relevant tissues will be evaluated to better understand CBD-mediated neuroimmune modulatory effects in males and females.Conclusions: Chronic postsurgical pain is a growing clinical problem. Current treatment strategies rely on opioid-based therapeutics, which affect patient quality of life and are associated with addiction and withdrawal. Treatment of nerve injuries with CBD could provide an effective alternative to manage NP. Understanding its mechanisms of action will provide important insights into the sex-dependent application of this nonpsychoactive cannabinoid, setting the groundwork for large-scale Canadian clinical trials in women and men presenting with chronic pain.

The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2–3 days and 7–8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7–8 days than at 2–3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2–3 days to 7–8 days post exercise (lower in 5 of the 6 subjects at 7–8 days than at 2–3 days; p<0.05). Thus, the increased fibre size at 7–8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

The side effects and safety of cannabidiol (CBD) products are currently discussed in different contexts. Of all adverse effects, hepatotoxic effects have been reported most frequently in previous studies. However, the threshold for liver toxicity of CBD in humans is uncertain due to the lack of adequately designed studies in humans below the lowest observed adverse effect level (LOAEL) of 300 mg/day. In a randomised, three-arm, double-blind, crossover study, the effects of two CBD products (oil and solubilisate (solu) containing 60 mg CBD) were investigated during a high-intensity exercise protocol. Seventeen well-trained subjects (26±4 years, 181±5 cm, 85.6±9.4 kg) participated in the intervention. All subjects were healthy and had no physiological or psychological injuries. Participants were divided into advanced (Ad) and highly advanced (Hi) athletes … They consumed 60 mg of the compound in each microcycle over 7 days. To evaluate possible effects of short-term repeated use of 60 mg CBD on oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), gamma-glutamyl transferase (GGT) and creatinine (CREA) were analysed before and after each microcycle. GOT increased significantly in both performance levels of the placebo groups (Ad: p≤0.001; Hi: p=0.003). This increase was significantly reduced in the Ad group by both CBD oil (p=0.050, ES=0.66) and CBD solu (p=0.027; ES=0.75). GPT also increased significantly in both placebo groups (Ad: p≤0.001; Hi: p=0.032). This increase was significantly reduced in the Ad group by both CBD oil (p=0.027; ES=0.75) and CBD solu (p=0.023; ES=0.77). These effects were not observed in the Hi group for either parameter. Our results show that short-term repeated use of 60 mg CBD can inhibit exercise-induced liver activity. Furthermore, under the conditions of the present study, there was no evidence for hepatotoxic effects of oral intake of CBD at 60 mg for seven days. Nevertheless, despite the inhibitory effect on exercise-induced liver activity, the study provides evidence for the pharmacological effects of CBD on the liver even at low CBD dose and does not exclude adverse effects in sensitive individuals.

Cholangiocarcinoma (CCA) is a rare and highly lethal disease with few effective treatment options. Cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) are non-psychedelic components extracted from cannabis. These non-psychoactive compounds have shown anti-proliferative potential in other tumor models; however, the efficacy of CBD and CBG in CCA is unknown. Furthermore, two cell death pathways are implicated with CBD resulting in autophagic degeneration and CBG in apoptosis. HuCC-T1 cells, Mz-ChA-1 cells (CCA cell lines) and H69 cells (immortalized cholangiocytes), were treated with CBD and CBG for 24 to 48 h. The influence of these cannabinoids on proliferation was assessed via MTT assay. Apoptosis and cell cycle were evaluated via Annexin-V apoptosis assay and propidium iodide, respectively. The expression of proliferation biomarker Ki-67, apoptosis biomarker BAX, and autophagic flux biomarkers LC3b and LAMP1 were evaluated via immunofluorescence. Cell migration and invasion were evaluated via wound healing assay and trans-well migration invasion assays, respectively. The colony formation was evaluated via colony formation assay. In addition, the expression of autophagy gene LC3b and apoptosis genes BAX, Bcl-2, and cleaved caspase-3 were evaluated via Western blot. CBD and CBG are non-selective anti-proliferative agents yielding similar growth curves in CCA; both cannabinoids are effective, yet CBG is more active at lower doses. Low doses of CBD and CBG enhanced immortalized cholangiocyte activity. The reduction in proliferation begins immediately and occurs maximally within 24 h of treatment. Moreover, a significant increase in the late-stage apoptosis and a reduction in the number of cells in S stage of the cell cycle indicates both CBD and CBG treatment could promote apoptosis and inhibit mitosis in CCA cells. The fluorescent expression of BAX and LC3b was significantly enhanced with CBD treatment when compared to control. LAMP1 and LC3b colocalization could also be observed with CBD and CBG treatment indicating changes in autophagic flux. A significant inhibition of migration, invasion and colony formation ability was shown in both CBD and CBG treatment in CCA. Western blot showed an overall decrease in the ratio of anti-apoptotic protein Bcl-2 with respect to pro-apoptotic protein BAX with CBG treatment. Furthermore, CBD treatment enhanced the expression of Type II cell death (autophagic degeneration) protein LC3b, which was reduced in CBG-treated CCA cells. Meanwhile, CBG treatment upregulated Type I cell death (programmed apoptosis) protein cleaved caspase-3. CBD and CBG are effective anti-cancer agents against CCA, capable of inhibiting the classic hallmarks of cancer, with a divergent mechanism of action (Type II or Type I respectively) in inducing these effects.

136 The effects of cannabidiol on libido and heart rate in stallions

New momentum in exploring marijuana's medical benefits: Marijuana has been lauded and lambasted for its potential effects on the body. In part 1 of a 2-part series, we investigate the accumulating evidence for the effectiveness of cannabis in treating some medical conditions.

Behavioural, pharmacokinetic, and genetic evidence of a cannabidiol-oxycodone drug-drug interaction in mice.

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

(360) Can CBD Reduce the Use of Pain Medication? Lessons from a Survey in a Pain Clinic Environment

Heavy alcohol consumption (Testa & Parks, 1996) and childhood sexual abuse (CSA; Messman-Moore & Long, 2003) have been associated with adult sexual victimization. We examined the social behavior of 42 women under two alcohol conditions (high dose and low dose) in a bar laboratory. Women were videotaped interacting with a man they had just met. Women in the higher dose condition engaged in more open body position and talked, stood, and walked more than women in the lower dose condition. These behaviors are consistent with signs of intoxication or romantic interest. The women in the high-dose condition also frowned more than women in the low-dose condition. An increase in frowning could indicate less comfort or may be considered consistent with an increase in animation during the social interaction given the concomitant increase in other behaviors. Thus, the nonverbal behavior of women in the high-dose condition could be interpreted as mixed signals. CSA victims exhibited fewer head movements (e.g., nods), were less animated, and frowned more than non-CSA victims. These behaviors convey reticence or possibly even anxiety or discomfort during the social interaction. Thus, the nonverbal behavior of women with a history of CSA may convey an unease that could be viewed by a potential perpetrator as vulnerability. Our findings suggest that both acute alcohol consumption and history of CSA may influence nonverbal social behavior and may influence risk for sexual assault by sending mixed cues of romantic interest or signs of vulnerability to potential perpetrators.

A descriptive study of older medical cannabis users in medical cannabis clinics

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today's scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.