Cannabidiol (CBD): One of the major phytocannabinoids in cannabis, non-psychoactive (does not get you high) but has proven efficacy in epilepsy, through randomized, placebo controlled clinical trials. May work in mono-therapy or adjunctively with other anti-epilepsy drugs. Will likely have an expanded profile of action in the brain when used with other cannabinoids, a so called “entourage effect”. Known to have anti-anxiety effects. Combinations of CBD and THC are being explored actively in disease treatment.
Cannabinoid receptors: Molecules with extracellular components that bind cannabinoids and mediate their intracellular effects. There are at least two known cannabinoid receptors, CB1 and CB2. More is known about the CB1 receptor, a fairly widespread pre-synaptic G-protein coupled receptor that inhibits cAMP and may increase the Ia K+ current. CB1 is found on pre-synaptic GABA and glutamate terminals inhibiting release of these neurotransmitters through blockade of both N and P/Q type pre-synaptic calcium channels. The phytocannbinoid THC but not CBD can activate these pre-synaptic receptors.
Cannabinoids: Any of a large number of organic substances found in the marijuana plant. Some of them are psychoactive, and most interact with the cannabinoid receptors.
Cannabis indica: A strain of Cannabis sativa, based primarily on morphology, with wide broad leaves, branches close together, deep green, short and bushy with dense flowers. Most cannabis plants typically have a mixture of indica and sativa. The more indica, the more “mellow” the psychotropic effects, while strains higher in sativa are purported to cause heightened awareness and cognitive stimulation. Indica strains are also associated with less anxiety than sativa. However, the morphologic criteria that distinguish the plants are less important than the molecule content of the plant. and a more sedating type of psychotropic effect.
Cannabis ruderalis: a strain of Cannabis sativa, a short plant with varied wide leaflets, thick stems, and minimal psychotropic effects. Ruderalis is known for its ability to flourish in harsh climates, its high CBD content, and its ability to auto flower 21 days after planting regardless of the light cycle.
Cannabis sativa: genus and species name of marijuana. The formal taxonomy is: Kingdom Plant, Phylum Magnoliophyta; Class Magnoliopsida; Order Rosales; Family Cannabaceae, Genus Cannabis, species sativa. A tall, light green, annual, herbaceous flowering plant with a stiff upright stem, 3-7 divided elongated and serrated narrow leaves, with pistillate flowers in spikes along the leafy stems. Overall gives more of a stimulant type psychotropic effect than its strains. It has been cultivated throughout recorded history as a source of fiber, seed oil, food, hemp (used in the manufacture of ropes and canvas), and psychoactive chemicals. The plant grows wild in all 50 states and in most countries throughout the world, though it likely originated in Asia. Archaeological and paleobotanical findings suggest that humans have used cannabis since the early Holocene period, approximately 11,000 years ago. In popular terms, known as marijuana. There are over 500 compounds in the plant, mostly terpenes, about 115 or so are cannabinoids, molecules that share similar structure and interact with the endocannabinoid system (see below).
Cannabis science: Cannabis research helps us understand how to use the cannabis flower and the molecules derived from it to treat symptoms of disease.
dronabinol (Marinol@) is a synthetic THC which has been approved for many years for chemotherapy-induced nausea and vomiting, and anorexia from AIDS or cancer. The onset of action is 30 minutes to 1 hour, with peak effect at 2 – 4 hours.
Edibles: Cannabis provided in “food” form, taken orally. Onset of action is slower (30-45 minutes), and the molecules undergo more extensive metabolism than inhaled cannabis. This can lead to higher brain levels of the drug, and various unique combinations of. cannabinoids with diverse effects. Interest in the additive or so called “entourage effects” of various cannabinoids, particularly those that modify the action of CBD, has recently increased.
Endocannabinoids: Naturally occurring substances in brain and other organs such as arachidonoylethanolamide (AEA or anandamide) and 2- arachodonoylglycerol (2-AG) which interact with cannabinoid receptors. There are many metabolic intermediate cannabinoid molecules also present in the cell. It is not clear how or if the majority of these cannabinoids produce an effect. AEA and 2-AG are manufactured in the post-synaptic cell, are released post-synaptically to exert retrograde actions on pre-synaptic neuron terminals. CB1 receptors are enriched in brain, while CB2 are enriched in immune cells, though also present in brain. The CB2 receptor is thought to exist only on post-synaptic cells. A very concise and timely review of these receptor actions can be found in: Lupica, C.R., et al., Cannabinoids as hippocampal network administrators, Neuropharmacology (2017), http:// dx.doi.org/10.1016/j.neuropharm.2017.04.003.
Endocannabinoid system: consists of the cannabinoid 1 receptor (CB1R) and cannabinoid 2 receptor (CB2R), other putative g-protein coupled receptors, intracellular effector molecules such as the cAMP cascade, endogenous cannabinoid ligands (endocannabinoids), metabolic intermediate molecules, and the enzymes involved in their synthesis, degradation, and transport
Hemp The Cannabis Sativa plant that has been cultivated and genetically engineered to contain little to no delta 9 THC.
Marijuana doctors (cannabis doctors): Providers that have special expertise in the use of Cannabis in disease. Since very little is known about how cannabis can truly work in disease, there are very few doctors with extensive knowledge in cannabis treatment.
Medical Cannabis (medicinal marijuana): Use of cannabis products in disease to alleviate symptoms. Synonymous with medical cannabis. Has been used to treat epilepsy, symptoms of multiple sclerosis, pain, anxiety, cancer induced nausea, AIDS wasting syndrome and other conditions. Very few placebo controlled, randomized, double blind studies have been conducted using marijuana, largely due to the prohibition of marijuana in 1937 and to the promotion of the idea in the 1980s that it is a “gateway” drug and has no medical value.
Medical marijuana dispensaries: Stores that sell medical cannabis to patients with “marijuana cards” (varies by state). These cards are typically authorized by a medical provider. No training or medical knowledge is required to operate a dispensary. Nor are dispensaries required to track side effects, adverse events, or poor outcomes.
Nabiximols (Sativex®) is an oral-mucosal spray of a formulated extract of the cannabis sativa plant that contains the principal cannabinoids THC and CBD as well as specific minor cannabinoids and other non-cannabinoid components. The active ingredients are absorbed in the lining of the mouth, either under the tongue or inside the cheek. GW Pharmaceutical Company and it’s licensing partners are commercializing Sativex for MS spasticity in 16 countries outside the United States. GW Pharma was recently acquired by Jazz Pharmacueticals.
Phytocannabinoids: The cannabinoids found in the cannabis plant, some of which are known to act on cannabinoid receptors. There are more than 100 identified phytocannabinoids.
Rimonabant: A synthetic cannabinoid. SR141716A was the first CB1 receptor antagonist and inverse agonist. Available in Europe since 2006 for use as an adjunct to diet and exercise for obese or overweight patients with associated risk factors. Sanofi-Aventis developed rimonabant in the US (Acomplia, Zimulti)) but it was not approved by the FDA due to the increased risk of psychiatric adverse events, including suicide. Data had shown a doubling of the risk of psychiatric disorders in patients taking Acomplia in comparison with placebo.
Synthetic cannabinoids: Pure cannabinoid molecules manufactured in a laboratory. In the US, there are only a few synthetic cannabinoids which are FDA approved for clinical use. Dronabinol (Marinol@) is a synthetic Δ9 THC which has been approved for many years for chemotherapy-induced nausea and vomiting, and anorexia from AIDS or cancer. The onset of action is 30 minutes to 1 hour, with peak effect at 2 – 4 hours. Nabilone (Cesamet@) is a synthetic Δ9 THC, DEA schedule 2, approved for chemotherapy induced nausea and vomiting. The vast majority of synthetics are use to pharmacologically characterize the endocannabinoid system. P-55,490 and WIN55,212 act as agonists at the CB1 receptor. JWH-133 is a synthetic cannabinoid with strong anti-angiogenic and anti-inflammatory activities. This agent is able to inhibit HIF-1 α, VEGF, MMPs, bFGF, IL-8, IL-17, and other mentioned cytokines and adhesion molecules both in vivo and in vitro. CP 55,940, is a non-selective partial agonist. Arachidonyl-2′-chlorethylamide (ACEA) is a selective high affinity CB1 agonist. HU-308, a Δ9-THC analog, is a highly selective CB2 agonist with nanomolar affinity at CB2 and > 1000 fold selectivity for CB2 vs. CB1. Virodhamine, arachidonic acid and ethanolamine joined by an ester linkage, has also been isolated and shown to act as a partial agonist at the CB1 receptor and a full agonist at the CB2 receptor; or CB1 receptor antagonist/inverse agonist (Steffens et al., 2005). Some of these synthetics are sprayed on other plant materials to make illicit and dangerous products like “spice” and “K2”.
Tetrahydrocannabinol (THC): The major psychoactive phytocannbinoid in marijuana. Works, at least in part, through interaction with the CB1 receptor. Delta 9 THC is the most potent psychotropic molecule in cannabis, delta 8 less so, none of the other molecules are thought to have significant psychotropic effects. This molecule is the object of harsh DEA regulation banning its use. However, when added to other cannabinoid molecules, it may enhance or alter its action, the so called “entourage effect”. Interaction with CBD is the most noted effect