CBD and THC: Do They Complement Each Other Like Yin and Yang?

Pennypacker, Sarah D.; Romero‐Sandoval, E. Alfonso

doi:10.1002/phar.2469

Cited by 31 publications

(20 citation statements)

References 71 publications

(270 reference statements)

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“…CBD lacks psychotropic activity, but is reported to reduce the adverse effects (anxiety, psychosis, etc.) of Δ 9 -THC ( Pennypacker and Romero-Sandoval, 2020 ). In addition to Δ 9 -THC and CBD, Cannabis sativa L. produces over 120 other phytocannabinoids as well as an abundance of related compounds including flavonoids, non-cannabinoid phenols, phenylpropanoids, fatty acids and terpenoids ( Hanus, et al, 2016 ; Gülck and Möller, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

2021

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The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.

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Section: Introductionmentioning

confidence: 99%

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

2021

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“…In order to carry out the first study aim, and based on our previous observations ( Pennypacker and Romero-Sandoval, 2020 ), we identified four clinically significant THC:CBD ratio categories: CBD can enhance THC effects (THC:CBD ratios ≥1:1), CBD has no significant effect on THC effects (ratios ∼1:2), CBD can either have no effect or is protective against THC effects (ratios 1:>2 < 6), or CBD is protective against THC effects (ratios ≤1:6). Products with THC:CBD ratios >0.7 were considered to fall into the first category, ≥1:1.…”

Section: Methodsmentioning

confidence: 99%

“…CBD has long been proven to alter cannabis’ effects, and while CBD data was presented alongside THC concentrations categories in our previous study, the data was not thoroughly analyzed in relation to THC:CBD ratios and concentrations ( Cash et al, 2020 ). Literature suggests that different concentrations of THC and CBD and different ratios of THC:CBD induce variances in experienced subjective effects ( Pennypacker and Romero-Sandoval, 2020 ). In fact, it appears that certain lower ratios of THC:CBD are more apt to produce an attenuation of THC induced effects ( Dalton et al, 1976 ; Englund et al, 2013 ; van de Donk et al, 2019 ) while higher ratios are more likely to enhance THC induced effects ( Arkell et al, 2019 ; Solowij et al, 2019 ; van de Donk et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, we wonder whether the combination of these high THC levels with certain CBD concentrations and/or the ratio of THC:CBD could result in a pharmacological interaction that reduces the risk of high levels of THC. We identified some products that are more pharmacologically amenable to medical purposes, based on their THC levels (i.e., <10%) ( Cash et al, 2020 ); but it is also possible that these products will contain THC:CBD ratios that lead to a pharmacologic interaction that enhances THC intoxicating effects ( Pennypacker and Romero-Sandoval, 2020 ). In other words, it is clinically relevant to garner whether or not the existing products contain these two cannabinoids at concentrations and ratios that are suitable for patients.…”

Section: Introductionmentioning

confidence: 99%

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Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot

et al. 2022

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Background and aims: The effects exuded by cannabis are a result of the cannabinoids trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), and is dependent upon their pharmacological interaction and linked to the two cannabinoids’ concentrations and ratios. Based on current literature and trends of increasing cannabis potency, we postulate that most medical cannabis products with THC and CBD have ratios capable of producing significant acute intoxication and are similar to recreational products. We will test this by organizing products into clinically distinct categories according to TCH:CBD ratios, evaluating the data in terms of therapeutic potential, and comparing the data obtained from medical and recreational programs and from states with differing market policies.Methods: We utilized data encompassing online herbal dispensary product offerings from nine U.S. states. The products were analyzed after being divided into four clinically significant THC:CBD ratio categories identified based on the literature: CBD can enhance THC effects (THC:CBD ratios ≥1:1), CBD has no significant effect on THC effects (ratios ∼ 1:2), CBD can either have no effect or can mitigate THC effects (ratios 1:>2 < 6), or CBD is protective against THC effects (ratios ≤1:6).Results: A significant number of products (58.5%) did not contain any information on CBD content. Across all states sampled, the majority (72–100%) of both medical and recreational products with CBD (>0%) fall into the most intoxicating ratio category (≥1:1 THC:CBD), with CBD likely enhancing THC’s acute effects. The least intoxicating categories (1:>2 < 6 and ≤1:6 THC:CBD) provided the smallest number of products. Similarly, the majority of products without CBD (0%) contained highly potent amounts of THC (>15%). These results were consistent, regardless of differing market policies in place.Conclusions: Despite the distinct goals of medical and recreational cannabis users, medical and recreational program product offerings are nearly identical. Patients seeking therapeutic benefits from herbal cannabis products are therefore at a substantial risk of unwanted side effects, regardless of whether they obtain products from medical or recreational programs. Efforts are needed to better inform patients of the risks associated with high potency cannabis and the interaction between THC and CBD, and to help shape policies that promote more therapeutic options.

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“…Among the identified components of cannabis, which are also called cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two major constituents. While THC is psychoactive and is closely related to addiction and toxic effects, CBD is nonpsychoactive and may modulate some of the effects of THC, though these interactive effects are largely dependent on several factors, such as dose ratio and time interval between the cannabinoids (Boggs et al, 2018; Pennypacker & Romero-Sandoval, 2020). Of note, there has been increasing interest in using CBD, with or without THC, to alleviate psychiatric and neurologic symptoms.…”

mentioning

confidence: 99%

Effect of cannabinoids on brain metabolites: A review of animal and human studies.

Ma¹,

Lyoo²,

Renshaw³

et al. 2023

Experimental and Clinical Psychopharmacology

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Cannabis has been widely used medically and recreationally for centuries. With a renewed interest in the therapeutic use of cannabinoids, which are active components of Cannabis sativa, it has become important to understand the cannabinoids’ neurobiological mechanisms related to both therapeutic and harmful effects. This review summarizes the effects of two major cannabinoids, delta-9-tetrahydrocannabinol and cannabidiol, on brain metabolites. We focus on human studies applying 1H-magnetic resonance spectroscopy (MRS) and animal studies using more invasive and direct methods to measure brain metabolites associated with glutamatergic neurotransmission or glial and neuronal functions. Although studies are limited in number, current evidence suggests that two major cannabinoids, which are thought to have differential effects on the brain, may alter the brain metabolite levels in distinct ways from each other. Potential limitations of present studies of cannabinoids on brain metabolites and suggestions regarding future studies are also discussed. We believe that issues clarified in this review may contribute to the design of future studies of cannabinoids on brain metabolites.

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CBD and THC: Do They Complement Each Other Like Yin and Yang?

Cited by 31 publications

References 71 publications

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot

Effect of cannabinoids on brain metabolites: A review of animal and human studies.

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