Analgesic and antiinflammatory activity of constituents of Cannabis sativa L

Department of Pharmacognosy, School of Pharmacy, University of London, England.
Inflammation (Impact Factor: 2.21). 09/1988; 12(4):361-71. DOI: 10.1007/BF00915771
Source: PubMed

ABSTRACT Two extracts of Cannabis sativa herb, one being cannabinoid-free (ethanol) and the other containing the cannabinoids (petroleum), were shown to inhibit PBQ-induced writhing in mouse when given orally and also to antagonize tetradecanoylphorbol acetate (TPA)-induced erythema of mouse skin when applied topically. With the exception of cannabinol (CBN) and delta 1-tetrahydrocannabinol (delta 1-THC), the cannabinoids and olivetol (their biosynthetic precursor) demonstrated activity in the PBQ test exhibiting their maximal effect at doses of about 100 micrograms/kg. delta 1-THC only became maximally effective in doses of 10 mg/kg. This higher dose corresponded to that which induced catalepsy and is indicative of a central action. CNB demonstrated little activity and even at doses in excess of 10 mg/kg could only produce a 40% inhibition of PBQ-induced writhing. Cannabinoid (CBD) was the most effective of the cannabinoids at doses of 100 micrograms/kg. Doses of cannabinoids that were effective in the analgesic test orally were used topically to antagonize TPA-induced erythema of skin. The fact that delta 1-THC and CBN were the least effective in this test suggests a structural relationship between analgesic activity and antiinflammatory activity among the cannabinoids related to their peripheral actions and separate from the central effects of delta 1-THC.

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    • "There are anecdotal reports of Cannabis relieving the sign and symptoms of various disease conditions such as asthma, convulsion, multiple sclerosis (MS), ocular pressure, acute post-operative and intractable pain, as well as stimulating appetite and antispasmodic (Russo, 2011; Ben, 2006; Hazekamp and Grotenhermen, 2010; Noyes et al., 1975; Wade et al., 2003; Grant, 2001; Tomida et al., 2006; Formukong et al., 1988; Obonga, 2006; Regelson et al., 1976; Di Tomaso et al., 1996). Other medicinal values such as antiemetic and use in palliative or terminal care have been reported for inhaled Cannabis and oral tetrahydrocannabinol (THC) (Matsuda **Corresponding author. "
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    ABSTRACT: As part of development efforts for a suitable dosage form, crude Cannabis resin was formulated into suppository dosage form using theobroma oil and the physical properties of the suppositories were evaluated. The following physical properties were evaluated: appearance (texture, presence or absence of entrapped air, contraction holes), liquefaction time, uniformity of weight and in-vitro release profile of the crude marijuana resin from the suppositories. The torpedo shaped suppositories were smooth in texture with absence of entrapped air and contraction holes. The suppositories had uniform greenish brown colour and low weight variation. The liquefaction time was also low. The 300 mg Cannabis crude in 4 % Tween 85 showed highest melting time (11.67 ± 057 min) while the incorporation of Tween 85 improved the release profile (0.0452-0.0650 %) in different batches. It is possible to formulate marijuana suppositories with satisfactory physical properties; however, release profile of marijuana from the suppository bases was generally low even though the addition of Tween 85 greatly enhanced drug release.
    African journal of pharmacy and pharmacology 11/2014; 8(44):1127-1131. DOI:10.5897/AJPP2014.4051 · 0.84 Impact Factor
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    • "tor agonist, supporting analgesic effects previously noted (Formukong et al., 1988), and moderate 5-HT1A antagonist suggesting antidepressant properties (Cascio et al., 2010). Normally, CBG appears as a relatively low concentration intermediate in the plant, but recent breeding work has yielded cannabis chemotypes lacking in downstream enzymes that express 100% of their phytocannabinoid content as CBG (de Meijer and Hammond, 2005; de Meijer et al., 2009a). "
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    ABSTRACT: Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL -1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
    British Journal of Pharmacology 08/2011; 163(7):1344-64. DOI:10.1111/j.1476-5381.2011.01238.x · 4.99 Impact Factor
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    • "Delta-9-Tetrahydrocannabinol (Δ 9 -THC) is the most prevalent and well characterized constituent of the approximately 70 cannabinoids identified in cannabis (Elsohly and Slade, 2005), and largely accounts for the psychoactive properties of this plant. Δ 9 -THC produces antinociceptive effects in a wide range of preclinical assays of pain, including tail-flick, hotplate, inflammatory, cancer, neuropathic, and visceral nociceptive models (Martin et al., 1984; Formukong et al., 1988; Burstein et al., 1988; Compton et al., 1991; Varvel et al., 2005). Visceral pain (e.g., myocardial ischemia, upper gastrointestinal dyspepsia, irritable bowel syndrome, and dysmenorrhea) is one of the most common forms of pain. "
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    ABSTRACT: Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Delta(9)-THC and CBN bound to the CB(1) receptor and produced antinociceptive effects. The CB(1) receptor antagonist, rimonabant, but not the CB(2) receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB(1) receptor with similar affinity as Delta(9)-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Delta(9)-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.
    Drug and alcohol dependence 09/2009; 105(1-2):42-7. DOI:10.1016/j.drugalcdep.2009.06.009 · 3.28 Impact Factor
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