Development Of Cannabinoids Research Articles

The Development of Cannabinoids as Therapeutic Agents in the United States.

Cannabis is one of the oldest and widely used substances in the world. Cannabinoids within the cannabis plant, known as phytocannabinoids, mediate cannabis' effects through interactions with the body's endogenous cannabinoid system. This endogenous system, the endocannabinoid system, has important roles in physical and mental health. These roles point to the potential to develop cannabinoids as therapeutic agents while underscoring the risks related to interfering with the endogenous system during nonmedical use. This scoping narrative review synthesizes the current evidence for both the therapeutic and adverse effects of the major (i.e., Δ9-tetrahydrocannabinol and cannabidiol) and lesser studied minor phytocannabinoids, from nonclinical to clinical research. We pay particular attention to the areas where evidence is well established, including analgesic effects after acute exposures and neurocognitive risks after acute and chronic use. In addition, drug development considerations for cannabinoids as therapeutic agents within the United States are reviewed. The proposed clinical study design considerations encourage methodological standards for greater scientific rigor and reproducibility to ultimately extend our knowledge of the risks and benefits of cannabinoids for patients and providers. SIGNIFICANCE STATEMENT: This work provides a review of prior research related to phytocannabinoids, including therapeutic potential and known risks in the context of drug development within the United States. We also provide study design considerations for future cannabinoid drug development.

Effect of High-Tunnel and Open-Field Production on the Yield, Cannabinoids, and Volatile Profiles in Industrial Hemp (Cannabis sativa L.) Inflorescence.

This study discovered the impact of high-tunnel (i.e., unheated greenhouse) and open-field production on two industrial hemp cultivars (SB1 and CJ2) over their yield parameters, cannabinoid development, and volatile profiles. Development of neutral cannabinoids (CBD, THC, and CBC), acidic cannabinoids (CBDA, THCA, and CBCA), and total cannabinoids during floral maturation were investigated. The volatile profiles of hemp flowers were holistically compared via HS-SPME-GC/MS. Findings indicated a high tunnel as an efficient practice for achieving greater total weight, stem number, and caliper, especially in the SB1 cultivar. Harvesting high-tunnel-grown SB1 cultivars during early flower maturation could obtain a high CBD yield while complying with THC regulations. Considering the volatile profiles, hemp flowers mainly consisted of mono- and sesquiterpenoids, as well as oxygenated mono- and sesquiterpenoids. Volatile analysis revealed the substantial impact of cultivars on the volatile profile compared to the production systems.

Modelling of the concentration—effect relationship of THC on central nervous system parameters and heart rate — insight into its mechanisms of action and a tool for clinical research and development of cannabinoids

Pharmacokinetics after pulmonary administration of delta-9-tetrahydrocannabinol (THC) and its major metabolites 11-OH-THC and 11-nor-9-COOH-THC was quantified. Additionally, the relationship between THC and its effects on heart rate, body sway and several visual analogue scales was investigated using pharmacokinetic-pharmacodynamic (PK-PD) modelling. This provided insights useful for the research and development of novel cannabinoids and the physiology and pharmacology of cannabinoid systems. First, the PK-PD model gave information reflecting various aspects of cannabinoid systems. The delay between THC concentration and effect was quantified in equilibration half-lives of 7.68 min for heart rate and from 39.2 to 84.8 min for the CNS responses. This suggests that the effect of THC on the different responses could be due to different sites of action or different physiological mechanisms. Differences in the shape of the concentration-effect relationship could indicate various underlying mechanisms. Second, the PK-PD model can be used for prediction of THC concentration and effect profiles. It is illustrated how this can be used to optimise studies with entirely different trial designs. Third, many new cannabinoid agonists and antagonists are in development. PK-PD models for THC can be used as a reference for new agonists or as tools to quantitate the pharmacological properties of cannabinoid antagonists.

Cannabinoids and analgesia

Cannabis extracts have been used medicinally for many thousands of years, including for pain relief. The identification of the major psychoactive component of cannabis, delta-9-tetrahydrocannabinol (Δ 9THC) and the subsequent identification of an endogenous cannabinoid system has led to an explosion in cannabinoid research. The substantial body of evidence for cannabinoid analgesia in various animal models of pain has not yet been confirmed in clinical studies. The major hurdles in the development of clinically useful cannabinoids are the separation of psychotropic and analgesic effects and the development of cannabinoids with sufficient bioavailability for a practical route of administration.