Archives: Research

An original investigation conducted by Arkell et al. assayed the effects of cannabidiol (CBD) compared to ∆⁹-Tetrahydrocannabidiol (THC) on driving performance. The study investigated the effects of vaporized THC-dominant versus CBD-dominant cannabis on driving performance; participants were between 20-50 years of age, had ample driving experience, reported infrequent cannabis use, but had at least 10 prior experiences with cannabis.

Participants received vaporized cannabis containing either 13.75 mg THC, a combination of 13.75mg THC & 13.75mg CBD (THC/CBD group), just 13.75mg CBD, or a placebo. Participants took a driving test on a 100-km highway circuit while maintaining a speed of 59 miles per hour and a steady lateral position (SDLP)–the distance between the vehicle and the lane boundary to the left of the vehicle, measured using an external apparatus. Cars were equipped with brakes for a licensed driving instructor who monitored safety.

The THC condition had a significantly increased SDLP compared to both the CBD condition and placebo (P < .001). There was no significant difference in SDLP between the CBD condition and placebo, indicating that CBD alone didn’t significantly alter driving performance. But 300 minutes after THC administration, there was no longer a significant difference in SDLP compared with placebo (P > .99) indicating that the effects had worn off. A secondary outcome, feeling ‘confident to drive’ was significantly decreased in the THC and THC/CBD condition (P < .001) compared to placebo, demonstrating observably altered subjective effects in the THC group. There was also a main effect of condition on performance on a cognitive task, the Digit Symbol Attention Task that measures processing speed and working memory. Overall, the THC group showed the most significant difference in performance, while the CBD-dominant cannabis failed to produce significant cognitive or psychomotor impairment, compared with placebo.

Regular use of cannabis high in delta-9-tetrahydrocannabinol (THC) is associated with increased risk of psychotic symptoms among young people. This finding has not been explored as deeply in adults who use cannabis-based medications. Velayudhan et al. conducted a meta-analysis to examine the correlation between usage of cannabis-based medications (CBMs) and neuropsychiatric adverse events using data from randomized clinical trials (RCTs) in people aged 50 years or older.

The analysis pooled data from RCTs using THC-only CBMs as well as CBD and THC combinations; the median age sampled was 58.2 years old. Results suggest significant positive association with incident rate ratios of dizziness or lightheadedness associated with cannabis-based medications, with THC dose as a moderator (p = .001). The analyses also found a positive correlation between the use of cannabis-based medications and incident rate ratios of thinking/perception disorders, moderated by THC dose (p <.001). However, higher THC dose was not associated with other neuropsychiatric adverse events in the randomized trials. The analyses results, while significant, faced some limitations such as use of self-reports and a lack of studies in populations older than 65 years of age.

Post-Traumatic Stress Disorder (PTSD) is characterized by intrusive memories of life-threatening events accompanied by severe anxiety and sleeplessness that often adversely affect quality of life. PTSD has been reported to have a life-time prevalence of 7-8%. With numerous individuals affected by PTSD, additional treatment options are warranted. In this double-blind, placebo-controlled study, the authors aim to examine the effects of elevated levels of anandamide through inhibition of Fatty Acid Amide Hydroxylase (FAAH) on fear extinction and affective stress response. Sixteen participants received 4mg of FAAH inhibitor and 29 participants received placebo daily for 10 days. Both groups underwent a battery of test to assess anandamide levels, response to stress, and fear extinction on days 9 and 10. There were no adverse events observed during the study period and participants who received the FAAH inhibitor had significantly higher levels of anandamide than those who received placebo. Interestingly, though FAAH inhibition had no effects on learning of conditioned fear, enhanced recall of fear extinction memory after 24 hours was observed in participants who received the inhibitor. However, this effect was not evident immediately within the learning session. Additionally, FAAH inhibition decreased stress-induced affective response without affecting baseline affect. Though the sample size is small, the results nevertheless provide evidence that increasing anandamide levels through FAAH inhibition is a plausible mechanism of action in the treatment of PTSD. Larger clinical trials are needed to further elucidate the role of anandamide in PTSD management.

pubmed.ncbi.nlm.nih.gov/31590924/

Cannabinoid receptor activation is known to ameliorate inflammatory bowel disease (IBD) in animal models, but the contributions of other factors in combination with receptor activation remain unstudied. Cannabinoids bind to G protein coupled receptors CB1 and CB2. Two widely known exogenous ligands for CB1 and CB2 are D⁹-tetrahydrocannabinol(THC) and cannabidiol (CBD). Becker et al. (2020) sought to understand the role of cannabinoids as well as the microbiome, hematopoietic cells, and enterocytes in the treatment of IBD/colitis.

Four groups of mice received either CBD (10 mg/kg), THC (10 mg/kg), THC+CBD (10 mg/kg, both) or vehicle control (VEH). Treatment began three days before researchers induced acute colitis by intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Researchers replicated their initial study with the same parameters by also inducing colitis with Dextran sulfate sodium (DSS).

THC and TCH+CBD significantly reduced inflammation and weight loss compared to CBD alone and VEH control in both models—assessed by colonoscopy, flow cytometry, histology, and detection of serum biomarkers. Analysis found THC alone as effective as THC+CBD in attenuating acute colitis, both in the DSS-induced and TNBS-induced models.

Significantly, THC-mediated increases in mucus were specific to the lining of the colon, illuminated by the finding that DSS mice treated with THC had gut leakage while TNBS mice did not. The study also found that THC’s attenuation of colitis was not dependent on changes in bacterial composition despite THC’s increase of gram-negative bacteria in the colon. This was affirmed by administering antibiotics to VEH or THC mice in a subsequent DSS-induced colitis model. Hematopoietic cannabinoid receptors were found, however, to mediate the THC-induced increases in TCA cycle and fatty acid metabolites.

In the TNBS-induced trial, VEH and CBD groups showed more immune cell infiltration and significant tissue damage compared to THC and THC+CBD groups; however, flow cytometry revealed CBD, THC, and CBD+THC groups reduced the number of cytotoxic T cells compared to VEH.

The study revealed a role of both CB1 and CB2 receptors in colitis models: THC treatment in  mice lacking either receptor had no effect. Overall, Becker et al. report a dynamic interplay between hematopoietic cells, enterocytes, immune cells, and cannabinoid receptor activation contributing to colitis improvement.

This study assesses cannabidiol, which inhibits the reuptake of endocannabinoids, as a treatment for cannabis use disorder.

Freeman et al. (2020) conducted a phase 2a, randomized, double-blind, placebo, controlled, clinical trial investigating the healing properties of cannabidiol for cannabis use disorder. Participants, aged 16-60, were selected based on their desire to stop using cannabis, but were also required to report an unsuccessful attempt to quit cannabis-use, as well as meet requirements for a positive THC-COOH urine sample. Participants were responsible for taking their medication throughout the study every twelve hours and were required to give urine samples in compliance with the study. Notably, all participants during this trial were given six motivational interviewing sessions led by trained psychologists, in addition to their cannabidiol treatment.

The study saved resources by using Bayesian modeling for dose predictions, comparing a given dose’s efficaciousness with that of placebo to predict optimal dosages. Cannabidiol efficaciousness was measured by a reduction in urinary THC-COOH: creatinine ratio and an increase in days per week abstaining from cannabis use. Initially, 48 participants enrolled and were randomly assigned to a placebo, 200mg, 400mg, or 800mg (1:1:1:1) treatment group. A second trial was run with 34 new participants, excluding the 200mg treatment group, as the probability of efficaciousness compared with placebo given observed data fell below the lower threshold of .1 (at .0082).

The analysis measured the absolute difference in treatment effects between treatment groups and placebo. The final analysis showed that cannabidiol 400mg and 800mg significantly decreased THC-COOH: creatinine ratios as well as increased days per week abstaining from cannabis use. Thus, cannabidiol, at the 400 and 800mg doses, has the potential to reduce cannabis use disorder. The analysis suggests that the 400mg dose is slightly more effective than the 800 mg dose, thus negating potential benefit of doses higher than 800mg.

Sickle cell disease affects approximately 100,000 Americans. It is a genetic disease characterized by chronic pain and extremely painful episodes, which usually require treatment with large doses of opioids for extended periods of time. Opioids have a long list of side effects including respiratory depression and the risk of addiction. Cannabis has shown promise in treating pain but few controlled human trials have investigated the therapeutic uses of cannabis in a rigorous way. This study evaluated the effects of an approximately 1:1 ratio of THC and CBD in vaporized cannabis, compared to a placebo control that contained no active drug. The participants were 23 persons with sickle cell disease who experienced chronic pain. Each participant completed treatment with both the THC and CBD containing vapor as well as the placebo vapor. Patients used opioids similarly throughout both legs of the trial (cannabis and placebo) and there were no adverse side effects reported with the cannabis treatment.  The trial concluded that vaporized cannabis did not significantly reduce pain and associated symptoms in comparison to placebo. The only statistically significant finding was that the cannabis treatment resulted in a decreased interference of sickle cell symptoms with mood.  Shortcomings of this study include its small sample size (23) and its short duration of treatment (5 days). Further investigations should be conducted to assess the utility of cannabis as a treatment for chronic pain, particularly since this work found no significant adverse effects with this drug. Better understanding how cannabis can and cannot effectively treat pain may help curb the ongoing opioid epidemic and may aid in safely managing chronic pain.

With increasing availability of cannabis products and its decriminalized status in many states, understanding its acute and residual effects on driving is important in promoting public health and in guiding law enforcement with implementations of legal limits. In this study, 96 participants were randomly assigned to placebo, low tetrahydrocannabinol (THC) or high THC groups. Measures including speed, lane control, heart rate, and subjective drug effects were obtained at 30 minutes, 24-, and 48hours after exposure to cannabis. Results showed group differences in speed 30 minutes after exposure but not at 24 or 48 hours. More specifically, individuals in the high THC group drove significantly slower than those in the placebo group but the low THC group did not vary from either the high THC group or the placebo group while completing the single task driving test. Interestingly, when distraction is added such as counting backwards while driving (dual task driving test) individuals in both high and low THC group significantly drove slower than those in the placebo group. On analyzing the results of lateral control (tendency to swerve) a significant group difference was observed at 48 hours but not at 24 hours or 30 minutes. The combined results of this study indicate that the acute effects of smoked marijuana correlates with driving slowly especially when a distraction is present. Although the results relating to swerving was inconclusive, it may be beneficial to investigate as to why lane control  is difficult to achieve at 48 hours after use but not acutely or 24 hours post exposure.

Cannabis has shown promise in treating several medical conditions but its effects on pregnant women and developing fetuses is unknown. This study aimed to investigate the association of self-reported cannabis use by pregnant women and unfavorable maternal and perinatal outcomes. The main outcome the researchers investigated was early preterm births amongst a cohort of 661,617 women. 6.1% of women who did not use cannabis experienced preterm births before 37 weeks in comparison to 12.0% of women who used cannabis during their pregnancy. The results indicate that pregnant women should not use cannabis during the weeks of their pregnancy or leading up to pregnancy. Nevertheless, future studies should be conducted to investigate the impact of cannabis on pregnant mothers and developing fetuses with respect to cannabis ingestion at different gestational stages. Further, the study reports that cannabis use amongst pregnant mothers is increasing. However, it is entirely possible that increases in self-reported cannabis use correlate more-so with cannabis decriminalization and reducing social stigma rather than an empirical increase in cannabis use amongst pregnant women.

This review article analyzed nine peer-reviewed studies focused on the effects of cannabinoids on Alzheimer’s disease and dementia. Due to the increasing life expectancy in society aging related Alzheimer’s disease onset has continued to increase since 1995. Thus, it is important that we investigate cannabis and its cannabinoids as potential pharmacotherapies for Alzheimer’s disease. The review of studies on CBD indicate that CBD can protect certain neuronal cells from pathological mechanisms present in Alzheimer’s disease. They also showed that CBD can promote neuronal cell growth in the hippocampus of the brain. Additionally, reviewed studies showed that the combination of CBD and THC appear to by more useful than CBD or THC alone in suppressing causal factors of Alzheimer’s disease. There should be continued research into CBD, THC, and other cannabinoids present in cannabis in order to determine their efficacy in preventing and treating Alzheimer’s disease.

Cannabidiol’s anxiolytic effects have been demonstrated in several studies. However, the mechanism for this effect remains to be elucidated. The present paper offers additional data that may aid in future research in understanding endocannabinoids’ role in anxious behaviors. Over 900 participants were recruited to take part in the genetic analysis of cannabinoid receptor two (CB2) in chromosome one. A polymorphism leading to an amino acid change from arginine to glycine (R63Q) was identified. Interestingly, individuals who maintained the genes coding for arginine scored higher in depression and anxiety scales. In addition, a single amino acid change from cysteine to alanine (C385A) was noted in the gene coding for fatty acid amide hydrolase (FAAH) which is an enzyme that degrades the endocannabinoid anandamide. Of note, individuals who have the R allele in CB2 and A allele in FAAH were found to have the highest scores on the psychometric scales that were used to determine depressive and anxious phenotypes. The genetic associations found in this study provides further justification for the need for more robust genetic studies in order to understand the endocannabinoid system’s role in psychiatric disorders.