Given the observed ability of CBD to be Cannabis terpenoids could offer. There is evidence to support a synergistic relationship between THC and CBD, In addition to THC and CBD, a third class of chemicals, called terpenoids, may This finding suggests the ability of CBD to bolster the medicinal effects of THC. While the synergy of CBD with THC has garnered significant investigation over the past Of particular note is the ability of “these aromatic compounds to contribute Taming THC: potential cannabis synergy and phytocannabinoid- terpenoid.
of CBD, Ability THC, and Terpenoids Synergistic
The sentiment was repeated by Calkins , who noted the suggestion of a friend in Tunis that lemon retained the confidence of cure of overdoses by cannabis users in that region. In his comprehensive review of cannabis in the first half of the 20th century, Walton once more supported its prescription Walton, Another traditional antidote to cannabis employing Acorus calamus Figure 3B is evident from the Ayurvedic tradition of India Lad, , p. Calamus root is the best antidote for the ill effects of marijuana.
This claim has gained credence, not only through force of anecdotal accounts that abound on the Internet, but with formal scientific case reports and scientific analysis McPartland et al.
Historical precedents also support pinene in this pharmacological role. If this be taken in myrrh and wine all kinds of phantoms beset the mind, causing laughter which persists until the kernels of pine-nuts are taken with pepper and honey in palm wine.
Of the components, palm wine is perhaps the most mysterious. Ethanol does not reduce cannabis intoxication Mello and Mendelson, However, ancient wines were stored in clay pots or goatskins, and required preservation, usually with addition of pine tar or terebinth resin from Pistacia spp.
Pine tar is rich in pinene, as is terebinth resin from Pistacia terebinthus ; Tsokou et al. Likewise, the pine nuts Figure 3C prescribed by Pliny the Elder harbour pinene, along with additional limonene Salvadeo et al.
Al-Ukbari also suggested pistachio nuts as a cannabis antidote in the 13th century Lozano, , and the ripe fruits of Pistacia terebinthus similarly contain pinene Couladis et al.
The historical suggestions for cannabis antidotes are thus supported by modern scientific rationales for the claims, and if proven experimentally would provide additional evidence of synergy Berenbaum, ; Wagner and Ulrich-Merzenich, Considered ensemble, the preceding body of information supports the concept that selective breeding of cannabis chemotypes rich in ameliorative phytocannabinoid and terpenoid content offer complementary pharmacological activities that may strengthen and broaden clinical applications and improve the therapeutic index of cannabis extracts containing THC, or other base phytocannabinoids.
Psychopharmacological and dermatological indications show the greatest promise. One important remaining order of business is the elucidation of mono- and sesquiterpenoid biosynthetic pathways in cannabis, as has been achieved previously in other species of plants Croteau, ; Gershenzon and Croteau, ; Bohlmann et al.
Various cannabis component combinations or cannabis extracts should be examined via high throughput pharmacological screening where not previously accomplished. Another goal is the investigation of the biochemical targets of the cannabis terpenoids, along with their mechanisms of action, particularly in the central nervous system.
Possible techniques for such research include radio-labelling of select agents in animals with subsequent necropsy. On a molecular level, investigation of terpenoid changes to phytocannabinoid signal transduction and trafficking may prove illuminating. While it is known that terpenoids bind to odorant receptors in the nasal mucosa Friedrich, and proximal olfactory structures Barnea et al.
Given that farnesyl pyrophosphate is a sesquiterpenoid precursor and the most potent endogenous agonist yet discovered for GPR92 McHugh et al. Behavioural assays of agents in animal models may also provide clues. Simple combinations of phytocannabinoids and terpenoids may demonstrate synergy as antibiotics if MICs are appreciable lowered Wagner and Ulrich-Merzenich, Ultimately, fMRI and single photon emission computed tomography studies in humans, with simultaneous drug reaction questionnaires and psychometric testing employing individual agents and phytocannabinoid-terpenoid pairings via vaporization or oromucosal application, would likely offer safe and effective methods to investigate possible interactions and synergy.
Should positive outcomes result from such studies, phytopharmaceutical development may follow. The development of zero-cannabinoid cannabis chemotypes de Meijer et al. Selective cross-breeding of high-terpenoid- and high-phytocannabinoid-specific chemotypes has thus become a rational target that may lead to novel approaches to such disorders as treatment-resistant depression, anxiety, drug dependency, dementia and a panoply of dermatological disorders, as well as industrial applications as safer pesticides and antiseptics.
A better future via cannabis phytochemistry may be an achievable goal through further research of the entourage effect in this versatile plant that may help it fulfil its promise as a pharmacological treasure trove. National Center for Biotechnology Information , U. Journal List Br J Pharmacol v. Author information Article notes Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Abstract Tetrahydrocannabinol THC has been the primary focus of cannabis research since , when Raphael Mechoulam isolated and synthesized it. The roots of cannabis synergy Cannabis has been a medicinal plant of unparalleled versatility for millennia Mechoulam, ; Russo, ; ; , but whose mechanisms of action were an unsolved mystery until the discovery of tetrahydrocannabinol THC Gaoni and Mechoulam, a , the first cannabinoid receptor, CB 1 Devane et al.
Table 1 Phytocannabinoid activity table. Open in a separate window. Selected possibilities for phytocannabinoid-terpenoid synergy Cannabis and acne AEA simulates lipid production in human sebocytes of sebaceous glands at low concentrations, but induces apoptosis at higher levels, suggesting that this system is under ECS control Dobrosi et al. Conclusions and suggestions for future study Considered ensemble, the preceding body of information supports the concept that selective breeding of cannabis chemotypes rich in ameliorative phytocannabinoid and terpenoid content offer complementary pharmacological activities that may strengthen and broaden clinical applications and improve the therapeutic index of cannabis extracts containing THC, or other base phytocannabinoids.
Click here to view. Safety evaluation of essential oils: Handbook of Essential Oils: Science, Technology, and Applications. Antibacterial cannabinoids from Cannabis sativa: Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all-trans-retinoic acid.
Antileishmanial activity of the terpene nerolidol. Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. J Pharmacol Exp Ther. Odorant receptors on axon termini in the brain.
Anti-inflammatory activity of oleoresin from Brazilian Copaifera. Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of - -linalool in mice. Antiparasitic compounds from East African plants: A toxicologic and dermatologic assessment of linalool and related esters when used as fragrance ingredients.
Recherches sur les proprietes pharmcodynamiques action sedative et action spasmolytique de quelques alcools terpeniques aliphatiques.
Proceedings 19th Annual Conference on the Cannabinoids. International Cannabinoid Research Society; Cannabidiol as a novel anti-acne agent? Cannabidiol inhibits lipid synthesis and induces cell death in human sebaceous gland-derived sebocytes; p.
Molecular targets for cannabidiol and its synthetic analogues: Bisset NG, Wichtl M. Herbal Drugs and Phytopharmaceuticals: Stuttgart; CRC Press; The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Neural basis of Deltatetrahydrocannabinol and cannabidiol: The Chemistry of Aromatherapeutic Oils. Orphan endogenous lipids and orphan GPCRs: Prostaglandins Other Lipid Mediat.
Chemistry and analysis of phytocannabinoids and other Cannabis constituents. Marijuana and the Cannabinoids. Biological activities of essential oils. Z Naturforsch [C] ; Fragrance compounds and essential oils with sedative effects upon inhalation. Opium and the Opium-Appetite: Composition and antimalarial activity in vitro of the essential oil of Tetradenia riparia. Hypnotic and antiepileptic effects of cannabidiol. Effects of marihuana in laboratory animals and in man.
Inhibition of an equilibrative nucleoside transporter by cannabidiol: Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist.
Proceedings 17th Annual Symposium on the Cannabinoids. Radical-scavenging activities of citrus essential oils and their components: J Agric Food Chem. Lea and Blanchard; On the natural history, action, and uses of Indian hemp. Red Eye Press; Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress. Sesquiterpene components of volatile oils as skin penetration enhancers for the hydrophilic permeant 5-fluorouracil. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain.
Comparative essential oil compostion of various parts of the turpentine tree Pistacia terebinthus growing wild in Turkey. J Sci Food Agric. Neural basis of anxiolytic effects of cannabidiol CBD in generalized social anxiety disorder: Biosynthesis and catabolism of monoterpenoids. In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds. The psychotomimetic effects of intravenous deltatetrahydrocannabinol in healthy individuals: Neurobehavioral actions of cannabichromene and interactions with delta 9-tetrahydrocannabinol.
Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.
Delgado P, Moreno F. Antidepressants and the brain. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Delta 9 -tetrahydrocannabinol. Denson TF, Earleywine M. Decreased depression in marijuana users. Determination and characterization of a cannabinoid receptor in rat brain. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
Deyo R, Musty R. Proceedings Symposium on the Cannabinoids. A cannabichromene CBC extract alters behavioral despair on the mouse tail suspension test of depression; p. Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptormediated signaling. Choice of drugs in the treatment of duodenal ulcer.
Crack heads and roots daughters: Chemical composition and antifungal properties of essential oils of three Pistacia species. Effects of Linalool on glutamatergic system in the rat cerebral cortex.
Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement.
A molecular link between the active component of marijuana and Alzheimer's disease pathology. Activity of cannabis in relation to its delta'-trans-tetrahydro-cannabinol content. Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation. Scand J Work Environ Health. J Toxicol Environ Health. Fan X, Gates RA. Degradation of monoterpenes in orange juice by gamma radiation. Fan X, Sokorai KJ. Changes in volatile compounds of gamma-irradiated fresh cilantro leaves during cold storage.
Chemical and biological evaluation of the essential oils of different Melaleuca species. Incorporation experiments with 13 C-labeled glucoses. Metabolic fingerprinting of Cannabis sativa L. Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. Franz C, Novak J. Sources of essential oils. Fride E, Russo EB. Schizophrenia, depression, and anxiety.
The Brain and Body's Marijuana and beyond. Effect of flavour components in lemon essential oil on physical or psychological stress. Modulation of effective connectivity during emotional processing by Delta9-tetrahydrocannabinol and cannabidiol. Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc. The structure and function of cannabigerol, a new hashish constituent.
Cannabichromene, a new active principle in hashish. Cannabigerol behaves as a partial agonist at both CB1 and CB2 receptors; p. Emerging roles for endocannabinoids in long-term synaptic plasticity. Metabolic costs of terpenoid accumulation in higher plants.
Gershenzon J, Croteau R. Lipid Metabolism in Plants. Anti-inflammatory cannabinoids in diet: Beta-caryophyllene is a dietary cannabinoid. Local anaesthetic activity of the essential oil of Lavandula angustifolia. Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck. Preliminary experiments on the chemistry and pharmacology of cannabis. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms.
The development of Sativex- a natural cannabis-based medicine. Cannabidiol and - Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Marijuana withdrawal in humans: Phytotherapeutic uses of essential oils.
Effects of oral THC maintenance on smoked marijuana self-administration. Cannabichromene and delta 9-tetrahydrocannabinol: Mono- and sesqui-terpene hydrocarbons of the eseential oil of Cannabis sativa.
Alkanes of the essential oil of Cannabis sativa. Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression? Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Delta-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. An endocannabinoid mechanism for stress-induced analgesia. Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of delta9-tetrahydrocannabinol.
Headspace volatiles of marijuana. Cannabinoid inhibition of adenylate cyclase: Kitab al-Yami' li-mufradat al-adwiya wa-l-agdiya. Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.
Central properties and chemcial composition of Ocimum basilicum essential oil. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. Percutaneous absorption of lavender oil from a massage oil. J Soc Cosmet Chem. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: J Pain Symptom Manage. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.
Attenuation of allergic contact dermatitis through the endocannabinoid system. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Treatment with lavender aromatherapy in the post-anesthesia care unit reduces opioid requirements of morbidly obese patients undergoing laparoscopic adjustable gastric banding.
Biological activities of Korean Citrus obovoides and Citrus natsudaidai essential oils against acne-inducing bacteria. Cannabis potency in Europe. Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Effects of citrus fragrance on immune function and depressive states. Chemical composition, antimicrobial and antioxidant activities of the essential oils of Sideritis erythrantha Boiss. Davis endemic in Turkey. Unlike myrcene, it has an inhibiting rather than augmenting effect.
Linalool is a sleep aid and an analgesic and has been used as an alternative therapy for chronic and acute pain. Linalool may help breast cancer patients by keeping tumors receptive to drugs.
This is extremely helpful since drug resistance is a major obstacle cancer patients face. Found in the rinds of citrus fruits, rosemary, peppermint, juniper, and pine needles, limonene is known for its use in perfumes, cleaning products, and medicines. Its therapeutic benefits are numerous. It has been used as an anti-inflammatory, antifungal, and an antibacterial. It helps alleviate bronchitis. It can reduce heartburn because of its ability to mitigate gastric reflux. In addition to these wonderful physical effects, it is known to make people happy; It is a stress reliever and mood enhancer.
Additionally, its anti-inflammatory properties may prove to be cancer preventative since inflammation plays an important role in the development of cancer cells.
You can find out the terpene profile of your flowers by purchasing labeled, lab-tested cannabis. You can also try the sniff test; remember, terpenes are what give cannabis flowers their aroma. If you like what you smell, try it out. Many of these plants have had traditional medicinal uses for hundreds of years.
Some of these traditional medicinal uses include calming or sleep-inducing effects basically the things that a sedative would be used for. Here is a list of terpenes that traditional use or modern research indicates have sedative or anxiolytic effects:.
This list is not exhaustive, but I believe it contains the most important ones. I will explore in the sections below whether there is any evidence to support the claims that these terpenes have sedative properties. I am lumping 5 of the terpenes together, because they seem to act in the same way. All have similar activities in rodents and all have a similar mechanism of action by working through the GABA system. Other sedative activities of terpinolene have not been tested.
GABA is the main inhibitory neurotransmitter in the brain and it exerts its effects through reducing neuronal excitability. They can bind to a distinct receptor site and act as positive allosteric modulators of GABA. In other words, they can increase activation of the receptor by GABA. For one, the pharmacologic profile of these terpenes is similar to that of benzodiazepines.
Flumazenil, which is an antagonist of the benzodiazepine binding site, blocks the effects of these terpenes in vitro and in vivo. Even though its pharmacology in rodents has not been characterized, we can assume that it will be similar to the other GABAergic terpenes. Catalepsy is the decreased ability to initiate movement. Another study indicated that chronic but not acute cannabis treatment in mice actually increased affinity of benzodiazepines for their binding site.
Since the GABAergic terpenes bind to this same site as benzodiazepines, it is possible that the anxiolytic effects of low doses of terpenes may be greater in chronic cannabis users. This does not negate the possibility that there is synergistic activity with lower doses of terpenes. Limonene has shown most of the classic sedative effects in animal studies. However, it did not show anxiolytic effects in the elevated plus maze test.
It also reversed many of the changes in in brain monoamine neurotransmitters induced by these stressors, including dopamine, norepinephrine, and serotonin. There were minimal changes in brain monoamine neurotransmitters and serum corticosterone in the absence of any stressor. However, limonene did partially block stress-induced increases in serum corticosterone.
The sedative mechanism of limonene may be multifaceted. Some but not all of the changes in brain monoamine neurotransmitters from limonene were reversed by flumazenil. In a study of monoamine neurotransmitter release from rat brain slices, the limonene metabolites perillic acid and perillyl alcohol acted more strongly than limonene itself. These metabolites may have a benzodiazepine-like activity at the GABA A receptor which limonene itself lacks. Caffeine, a known stimulant, is an antagonist of this receptor along with the other adenosine receptor subtypes.
The adenosine A 2A receptor can regulate glutamate, GABA, and dopamine release, so this may be another mechanism through which limonene regulates neurotransmitter release.
Sedative and Anxiolytic Effects of Cannabis Terpenes
Cannabinoids like CBD and THC have received the bulk of the press in effect," as it is generally known, refers to terpenes reacting synergistically with linalool could have is its ability to help with convulsions in seizures. Whereas terpenes are generally credited with giving pot its varied fragrances— limonene, for example, The idea that botanical marijuana creates a synergistic chemical effect, fingerprinting the “The biggest influence [in the entourage effect] is CBD,” says “It interferes with their ability to function. Terpenes are abundant in cannabis and cannabis oils (CBD oil). that also needs the CBD oil for the anti-inflammatory abilities of CBD.