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Herbs with Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
The final complication is that there are many cannabinoids, terpenoids, and other phytochemicals contained in the cannabis plant, and they may act in quite different fashion from one another. The composition of phytochemicals can vary from one strain of cannabis to another, with some containing high concentrations of THC and others containing high concentrations of cannabinoids such as CBD that buffer THC.35 These different cannabinoids may also interact with each other through the so-called “entourage effect” and thus possibly create new and unexpected effects.36 It is entirely possible that strains of cannabis that are high in CBD may offer benefits that are not seen in those that are high in THC. Indeed, psychiatrically, CBD appears to be the most helpful component of cannabis. Nonetheless, at the present time, cannabis cannot be recommended as a treatment for MDD.
Why Terpenes Matter—The Entourage Effect
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
There is a lot more to cannabis than its cannabinoid content. Other therapeutic compounds in cannabis contribute to its smell and aromatic diversity. Terpenes have garnered increased attention as a result of the “entourage effect” which emphasizes that the therapeutic benefits of cannabis are improved when full spectrum compounds—multiple cannabinoids + terpenoids + flavonoids—are used instead of single cannabinoids. The terms terpene and terpenoid are frequently used interchangeably, but they have different meanings. Terpenes are hydrocarbons (the only elements present are hydrogen and carbon), whereas terpenoids have been denatured by oxidation—drying and curing the flowers or chemically modified.
Use of Cannabinoids in Palliative Nutrition Care
Published in Victor R. Preedy, Handbook of Nutrition and Diet in Palliative Care, 2019
Understanding what makes cannabis unique requires knowledge of the human-endocannabinoid system. This system is composed of cannabinoid receptors, endogenously produced cannabinoids (endocannabinoids) and the enzymes responsible for their synthesis and deactivation (Vemuri and Makriyannis 2015). The primary cannabinoid receptors, termed CB1 and CB2, exhibit different distribution patterns with CB1 present primarily in the nervous system and CB2 present primarily in peripheral and immune tissues (Battista et al. 2012). Via interaction with these receptors, endocannabinoids exert effects on various physiological processes including immune, metabolic, hormonal and cognitive and behavioral functions, to name a few (Battista et al. 2012). Phytocannabinoids are plant-derived substances that interact with the endocannabinoid system and/or share similar chemical structure to cannabinoids (Gertsch et al. 2010). The cannabis plant contains over 120 phytocannabinoids, as well as terpenoids, both of which exert a wide variety of physiologic effects and account for interest in its medicinal use (Russo 2011; Morales et al. 2017). It is thought that synergistic effects of cannabis’ phytocannabinoids and terpenoids may be responsible for the belief that use of the whole plant is more effective than use of individual synthesized or extracted cannabinoids for desired medicinal effects. This concept of cannabis synergism has been termed “the entourage effect” (Russo 2011).
Medicinal cannabis pharmacokinetics and potential methods of delivery
Published in Pharmaceutical Development and Technology, 2022
Lidya Kebede, Seyedehsara Masoomi Dezfooli, Ali Seyfoddin
The entourage effect is not only observed in exogenous cannabinoids but is also demonstrated by endogenous compounds in our body (Fowler 2003). A review that discusses the neuroprotective effects of cannabinoids, suggests that plant-derived compounds are not the only ones that have an entourage effect, but endogenous cannabinoid and related compounds also experience the same phenomena. Anandamide is a well-studied endocannabinoid that is part of the N-acyl ethanolamines group (Fowler 2003). When anandamide was studied on peripheral polymodal nociceptors in normal and inflamed knee joints in rats, its ability to activate vanilloid and cannabinoid receptors was observed (Gauldie et al. 2001). Anandamide’s affinity to those receptors was further increased when used in conjunction with other N-acyl ethanolamines (Fowler 2003). A study that had discovered a new family of bioactive molecules, the arachidonyl amino acids, in the mammalian brain in 2001, had also provided evidence of synergistic interaction between anandamide and arachidonyl-glycine. Arachidonyl-glycine, unlike anandamide, lacks affinity to CB1 and vanilloid VR1 receptors but can suppress tonic pain. When these two molecules are present, they maintain spontaneous pain, allodynia, and hyperalgesia by minimising central sensitisation and leading to reduced pain following an injury (Huang et al. 2001).
The association of cannabis use and cardiac dysrhythmias: a systematic review
Published in Clinical Toxicology, 2020
John R. Richards, Eike Blohm, Kara A. Toles, Angela F. Jarman, Dylan F. Ely, Joshua W. Elder
In our review, 28 (42%) of the 67 total articles (and nearly half of the case series and reports) on the association of cannabis use and cardiac dysrhythmia were published from 2010 to present. This likely reflects the modern-day selective breeding techniques of phytogenic cannabis and cultivation practices that has resulted in much higher THC potency compared to historic concentrations [86]. This increasing ratio of THC relative to other cannabinoids and terpenes present in phytogenic cannabis which may have medical benefit, such as cannabidiol (CBD), may negate this “entourage effect” and have potential for increased cardiac and central nervous system toxicity [88]. Despite this increase in THC potency, there exist millions of cannabis users who presumably have never experienced cardiac dysrhythmia, suggesting a relative safety of cannabis compared to other recreational drugs and alcohol. Similar to cannabinoid hyperemesis syndrome, there may be a small subset of individuals with rare pharmacogenetic profiles who are at risk for cannabis-induced cardiac dysrhythmia [70].
The ‘entourage effect’ or ‘hodge-podge hashish’: the questionable rebranding, marketing, and expectations of cannabis polypharmacy
Published in Expert Review of Clinical Pharmacology, 2020
Herein is an assessment of the entourage effect, aimed at establishing what, if any, reason there is for speaking of it as some general or predictive phenomenon that can reliably be expected to bring therapeutic value (i.e. increased benefit or decreased risk) beyond any single component of the cannabis plant in isolation. The perspective offered is not intended as a simple review of the primary literature, nor does it pretend to be a balanced presentation of all available data or pertinent concerns. Rather it is a survey of the same literature used to argue assumptions of entourage benefit with the intent of questioning if such assumptions are indeed justified by the evidence presented therein [3,4,5]. The goal is to encourage accountability amongst academicians, healthcare professionals, and industry representatives in how we report and discuss speculative, contentious, or even dubious claims that are likely to be abused to the detriment of the public at large and to encourage legislators and regulators to turn an eye toward these same abuses.