- In Vitro Screening of Three Commercial Cannabis-Based Products on ATP-Binding Cassette and Solute-Carrier Transporter Function
Cannabis-based products are being used in combination with conventional drugs to treat a variety of health conditions, therefore there is increased potential for drug-drug interactions (DDIs). Since DDIs can lead to serious adverse events, drug regulatory bodies require that every investigational drug be evaluated for DDI potential at metabolic enzymes and transporters. However, this seldom occurs for cannabis-based products due to legislation in many jurisdictional allowing a direct pathway to market. This study aimed to examine the inhibitory potential of Spectrum Yellow, Tweed Argyle, and Spectrum Red at human ATP-binding cassette (ABC) and solute-carrier (SLC) transporters using in vitro models. We found that Tweed Argyle inhibited ABCB11 transport, however the unrealistically high dose to achieve inhibition suggests that a clinically significant DDI is unlikely. Spectrum Yellow and Tweed Argyle inhibited ABCG2, in line with previous studies. However, inhibition of ABCG2 is unlikely at therapeutically relevant doses. To date, clinically significant DDIs between cannabis-based products and BCRP substrates have not been reported. Read the full study.
- Effect of cannabidiol on the long-term toxicity and lifespan in the preclinical model C. elegans
In the C. elegans model, CBD did not demonstrate any degree of acute or life-long toxicity or related liabilities at physiologically relevant concentrations. Indeed, CBD extended mean lifespan up to 18% and increased late-stage life activity by up to 206% compared to controls. At low (10µM) and medium (40µM) concentrations, CBD attenuated age-related declines in motility at Days 12 and 15. Acute toxicity assays with CBD did not have a significant impact on C. elegans survival or motility, with the exception of 4000 µM CBD, which significantly reduced motility; however, this concentration is at least ten times outside of physiologically relevant concentrations. Read the full study.
- Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs
Emerging safety and/or tolerability studies in dogs reveal that CBD generally has a favorable safety profile and is well tolerated. However, there are no published studies on systemic levels of CBD following repeated dosing with <5 mg/kg/day, nor on CBD pharmacokinetics following a period of repeated dosing. Moreover, published studies have utilized proprietary and/or ill-defined distillate formulations rather than highly purified CBD. The objectives of this study were 1) to determine the safety profile of four different doses of CBD isolate (1, 2, 4, or 12 mg/kg/day; PO), administered once daily for 28 days in canines; and, 2) to ascertain the effect of repeated administration of different dose levels on the PK profile of CBD and two metabolites, namely 7-COOH-CBD and 7-OH-CBD. Read the full study.
- Safety, Pharmacokinetic, and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participants
Due to inadequate or lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of marketed medical cannabis products is limited. The objective of this study was to evaluate the safety, tolerability, PK and PD of Spectrum Yellow oil (20 mg/mL cannabidiol (CBD) and 0.9 mg/mL delta-9-tetrahydrocannabinol (THC). Read the full study.
- Safety, Pharmacokinetic, and Pharmacodynamics of Spectrum Red Softgels in Healthy Participants
Due to inadequate or lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of marketed medical cannabis products is limited. The objective of this study was to evaluate the safety, tolerability, PK and PD of Spectrum Red softgels (2.5 mg delta-9-tetrahydrocannabinol (THC), < 0.25 mg cannabidiol (CBD)). Read the full study.
- Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study
Cannabichromene (CBC) is particularly abundant in cannabis and has displayed anti-microbial, anti-inflammatory, analgesic, and antidepressant-like activity in rodents, but its effects in humans have not been directly examined. This study presents findings from a secondary analysis of data from our pharmacokinetic (PK) study of Spectrum Yellow oil. Read the full study.
- Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec
This is an observational study of 585 adult patients who were authorized a medical cannabis product from Spectrum Therapeutics™ and followed every 3 months for 12 months at Santé Cannabis, a network of medical cannabis clinics in Quebec, Canada, between October 2017 and August 2019. Symptom improvements over time were observed for pain, tiredness, drowsiness, anxiety, and well-being (ps<.05). Patients authorized THC-dominant products exhibited less symptom improvement for anxiety and well-being relative to those authorized CBD-dominant products (ps<.05). No serious adverse events were reported. Read the full study.
- Cannabinoid Profiles in Medical Cannabis Users: Effects of Age, Gender, Symptoms and Duration of Use
The aims of this observational study were to describe patterns of medical cannabis use and associated changes in symptom severity and to evaluate change in cannabis dose over time for pain-related symptoms. Data were collected by Strainprint™, an application that is HIPAA, PIPEDA, and PHIPA compliant. A total of 629 participants recorded data between May 2017-Aug. 2019. THC-dominant products were more frequently consumed for symptoms of pain and sleep, while CBD-dominant products were more frequently consumed for anxiety and depression. Male and female participants demonstrated significant differences in the type of cannabis they consumed. Dosages of CBD-dominant and balanced (THC:CBD) products increased over time irrespective of symptom response. THC-dominant products demonstrated a significant relationship between dose and symptom reduction over time. Our study provides real-world insights into how participants use and respond to cannabis products, and suggests that THC is used for pain control, in a dose-dependent manner. Read the full study.
- A crowdsourcing survey study on the subjective effects of delta-8-tetrahydrocannabinol relative to delta-9-tetrahydrocannabinol and cannabidiol
This study queried Δ8-THC users about product use characteristics and self-reported drug effects. Compared to Δ9-THC, self-reported ratings for “Drug effect,” “Bad effect,” “Sick,” “Anxiety,” “Paranoia,” “Irritability,” “Restlessness,” “Memory Problems,” and “Trouble Performing Routine Tasks” were lower for Δ8-THC (d = -0.21 to -0.44). Compared to CBD, ratings for Δ8-THC effects were higher for “Drug effect,” “Good effect,” “High,” “Relaxed,” “Sleepy,” “Hunger/Have the Munchies,” “Memory Problems,” “Trouble Performing Routine Tasks,” and “Paranoia” (d = 0.27-1.02). Qualitative responses indicated that participants used Δ8-THC because it is perceived as (a) legal, (b) a substitute or similar to Δ9-THC, and/or (c) less intense than Δ9-THC. Read the full study.
- Practical Considerations for Testing the Effects of Cannabidiol on Human Anxiety
Empirical evidence continues to accumulate suggesting cannabidiol (CBD) may have potential as an anxiolytic. Yet, research in the area is insufficient to support strong inferences. Accordingly, there is a need for additional empirical investigation. Research on the effects of CBD and anxiety requires a working knowledge of both. Understanding of contemporary CBD and anxiety research methods is critical to safely and convincingly test predictions regarding potential anxiolytic effects of CBD. The current paper outlines major design, methods, and safety considerations pertinent both to CBD administration and measuring effects on anxiety outcomes in order to facilitate needed research in this domain. Read the full paper.