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Cannabis is more than simply Delta(9)-tetrahydrocannabinol

Psychopharmacology (2003) 165:431–432
DOI 10.1007/s00213-002-1348-z
Ethan B. Russo · John M. McPartland
Cannabis is more than simply D
Received: 13 August 2002 / Accepted: 30 October 2002 / Published online: 19 December 2002
Springer-Verlag 2002
In response to your recent publication comparing
subjective effects of D
-tetrahydrocannabinol and herbal
cannabis (Wachtel et al. 2002), a number of comments are
necessary. The first concerns the suitability of the chosen
“marijuana” to assay the issues at hand. NIDA cannabis
has been previously characterized in a number of studies
(Chait and Pierri 1989; Russo et al. 2002), as a crude low-
grade product (2–4% THC) containing leaves, stems and
seeds, often 3 or more years old after processing, with a
stale odor lacking in terpenoids. This contrasts with the
more customary clinical cannabis employed by patients in
Europe and North America, composed solely of unseeded
flowering tops with a potency of up to 20% THC.
Cannabis-based medicine extracts (CBME) (Whittle et al.
2001), employed in clinical trials in the UK (Notcutt
2002; Robson et al. 2002), are extracted from flowering
tops with abundant glandular trichomes, and retain full
terpenoid and flavonoid components.
In the study at issue (Wachtel et al. 2002), we are
informed that marijuana contained 2.11% THC, 0.30%
cannabinol (CBN), and 0.05% (CBD). The concentration
of the latter two cannabinoids is virtually inconsequential.
Thus, we are not surprised that no differences were seen
between NIDA marijuana with essentially only one
cannabinoid, and pure, synthetic THC. In comparison,
clinical grade cannabis and CBME customarily contain
high quantities of CBD, frequently equaling the percent-
age of THC (Whittle et al. 2001).
Carlini et al. (1974) determined that cannabis extracts
produced effects “two or four times greater than that
expected from their THC content, based on animal and
human studies”. Similarly, Fairbairn and Pickens (1981)
detected the presence of unidentified “powerful syner-
gists” in cannabis extracts, causing 330% greater activity
in mice than THC alone.
The clinical contribution of other CBD and other
cannabinoids, terpenoids and flavonoids to clinical can-
nabis effects has been espoused as an “entourage effect”
(Mechoulam and Ben-Shabat 1999), and is reviewed in
detail by McPartland and Russo (2001). Briefly summa-
rized, CBD has anti-anxiety effects (Zuardi et al. 1982),
anti-psychotic benefits (Zuardi et al. 1995), modulates
metabolism of THC by blocking its conversion to the
more psychoactive 11-hydroxy-THC (Bornheim and
Grillo 1998), prevents glutamate excitotoxicity, serves
as a powerful anti-oxidant (Hampson et al. 2000), and has
notable anti-inflammatory and immunomodulatory effects
(Malfait et al. 2000).
Terpenoid cannabis components probably also con-
tribute significantly to clinical effects of cannabis and boil
at comparable temperatures to THC (McPartland and
Russo 2001). Cannabis essential oil demonstrates seroto-
nin receptor binding (Russo et al. 2000). Its terpenoids
include myrcene, a potent analgesic (Rao et al. 1990)
and anti-inflammatory (Lorenzetti et al. 1991), beta-
caryophyllene, another anti-inflammatory (Basile et al.
1988) and gastric cytoprotective (Tambe et al. 1996),
limonene, a potent inhalation antidepressant and immune
stimulator (Komori et al. 1995) and anti-carcinogenic
(Crowell 1999), and alpha-pinene, an anti-inflammatory
(Gil et al. 1989) and bronchodilator (Falk et al. 1990).
Are these terpenoid effects significant? A dried sample
of drug-strain cannabis buds was measured as displaying
an essential oil yield of 0.8% (Ross and ElSohly 1996), or
a putative 8 mg per 1000 mg cigarette. Buchbauer et al.
(1993) demonstrated that 20–50 mg of essential oil in the
ambient air in mouse cages produced measurable changes
in behavior, serum levels, and bound to cortical cells.
Similarly, Komori et al. (1995) employed a gel of citrus
fragrance with limonene to produce a significant antide-
pressant benefit in humans, obviating the need for
continued standard medication in some patients, and also
improving CD4/8 immunologic ratios. These data would
E. B. Russo (
Montana Neurobehavioral Specialists,
900 North Orange Street, Missoula, MT, 59802 USA
J. M. McPartland
Faculty of Health and Environmental Science,
Private Bag 92025, Mt Albert, Auckland, New Zealand
strongly support a demonstrable clinical role for cannabis
Flavonoid components of cannabis, especially likely to
be of benefit in oral or sublingual administration, include
apigenin, a unique agent that has strong anti-anxiety
effects without sedation (Salgueiro et al. 1997).
Finally, although anecdotal, this author (E.B.R.) has
had the opportunity to interview an estimated 200 patients
who have employed Marinol and clinical cannabis,
whether smoked or ingested. In no instance were the
effects of the former considered of equal efficacy to
cannabis, but rather more productive of dysphoric and
sedative adverse effects (Calhoun et al. 1998).
In essence, clinical cannabis demonstrates herbal
synergy and is more than a simply a vehicle for THC
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... New approaches are thus needed to either modulate/improve the side effects of cannabis/D 9-THC use or to produce pain relief without these side effects. One such potential class of compounds is terpenes, which may also contribute to the overall effect of cannabis (Russo and McPartland, 2003;Nuutinen, 2018;Booth and Bohlmann, 2019). ...
... Several scientific attempts have been made to classify cannabis plants based on their phytochemical composition. Cannabis products used for medicinal purposes usually contain a high content of the biologically active D 9 -THC, but it is becoming clear that multiple cannabis compounds are involved in its various therapeutic effects (Russo and McPartland, 2003). High-throughput genotyping of a diverse collection of cannabis germplasm showed that genetic differences between hemp and marijuana are not limited to genes involved in D 9 -THC production (Sawler et al., 2015). ...
... Initial speculation of the entourage effect came after a study found endogenous lipids were able to modulate the activity of an endogenous cannabinoid (Ben-Shabat et al., 1998). Subsequent investigation came in the form of perspective reviews (Russo and McPartland, 2003;Russo, 2011;Russo and Marcu, 2017), as well as investigating the interactions between different phytocannabinoids, mostly CBD and D 9 -THC (Johnson et al., 2010;Casey et al., 2017;Pamplona et al., 2018). However, more recently, a variety of studies have examined the role of terpenes in phytocannabinoid-mediated antitumor activity (Blasco-Benito et al., 2018), cell cytotoxicity (Namdar et al., 2019), and direct interactions with cannabinoid receptors (Santiago et al., 2019;Finlay et al., 2020). ...
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Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics. Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief. Cannabis sativa contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ9-THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes β-myrcene, α-pinene, limonene, and linalool, as well as the sesquiterpenes β-caryophyllene and α-humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects. The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management. SIGNIFICANCE STATEMENT: Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.
... e species Cannabis sativa L. includes three subspecies: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. e unique therapeutic effects of cannabis are hypothesized to be achieved through a complex synergy between the multiple phytocannabinoids and many other secondary compounds of the plant, including terpenes and flavonoids [6,7]. Cannabinoids are the subject of ongoing active research in the field of natural pharmaceutical agents, with evidence implying their potential effectiveness for the treatment of inflammation, cancer, and cardiovascular disorders [8][9][10]. ...
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Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver abnormalities and has been linked with metabolic syndrome hallmarks. Unfortunately, current treatments are limited. This work aimed to elucidate the effects of three cannabis extracts on metabolic alteration and gut microbiota composition in a mouse model of NAFLD and obesity. Male mice were fed with a high-fat diet (HFD) for 12 weeks. Following the establishment of obesity, the HFD-fed group was subdivided into HFD or HFD that was supplemented with one of three cannabis extracts (CN1, CN2, and CN6) for additional 8 weeks. Metabolic parameters together with intestinal microbiota composition were evaluated. Except for several minor changes in gene expression, no profound metabolic effect was found due to cannabis extracts addition. Nevertheless, marked changes were observed in gut microbiota diversity and composition, with CN1 and CN6 exhibiting microbial abundance patterns that are associated with more beneficial outcomes. Taken together, specific cannabis extracts’ addition to an HFD results in more favorable modifications in gut microbiota. Although no marked metabolic effect was disclosed, longer treatments duration and/or higher extracts concentrations may be needed. More research is required to ascertain this conjecture and to establish the influence of various cannabis extracts on host health in general and NAFLD in particular.
... In recent years, due to increasing awareness of the plants' potential for modern medicine, its cultivation is spreading worldwide for the rapidly evolving medical cannabis industry (Decorte and Potter, 2015;Chouvy, 2019). Drug-type medical cannabis plants yield inflorescences rich in hundreds of phytochemicals such as cannabinoids, terpenoids, and flavonoids, which are the source of the plants' biological activity (Russo et al., 2003;Andre et al., 2016;Shapira et al., 2019). The biosynthesis of these secondary metabolites is affected by environmental and cultivation conditions (Magagnini et al., 2018;Bernstein et al., 2019aBernstein et al., , 2005Danziger and Bernstein, 2021a,b;Rodriguez-Morrison et al., 2021;Westmoreland et al., 2021); and the increasing demand by the pharmacological industry for a high-quality chemically standardized plant product requires understanding of the plant physiological and metabolic responses to exogenous factors, which is very limited today. ...
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The N form supplied to the plant, ammonium (NH4+) or nitrate (NO3–), is a major factor determining the impact of N nutrition on plant function and metabolic responses. We have hypothesized that the ratio of NH4/NO3 supplied to cannabis plants affects the physiological function and the biosynthesis of cannabinoids and terpenoids, which are major factors in the cannabis industry. To evaluate the hypothesis we examined the impact of five supply ratios of NH4/NO3 (0, 10, 30, 50, and 100% N-NH4+, under a uniform level of 200 mg L–1 N) on plant response. The plants were grown in pots, under controlled environment conditions. The results revealed high sensitivity of cannabinoid and terpenoid concentrations and plant function to NH4/NO3 ratio, thus supporting the hypothesis. The increase in NH4 supply generally caused an adverse response: Secondary metabolite production, inflorescence yield, plant height, inflorescence length, transpiration and photosynthesis rates, stomatal conductance, and chlorophyll content, were highest under NO3 nutrition when no NH4 was supplied. Ratios of 10–30% NH4 did not substantially impair secondary metabolism and plant function, but produced smaller inflorescences and lower inflorescence yield compared with only NO3 nutrition. Under a level of 50% NH4, the plants demonstrated toxicity symptoms, which appeared only at late stages of plant maturation, and 100% NH4 induced substantial plant damage, resulting in plant death. This study demonstrates a dramatic impact of N form on cannabis plant function and production, with a 46% decrease in inflorescence yield with the increase in NH4 supply from 0 to 50%. Yet, moderate levels of 10–30% NH4 are suitable for medical cannabis cultivation, as they do not damage plant function and show only little adverse influence on yield and cannabinoid production. Higher NH4/NO3 ratios, containing above 30% NH4, are not recommended since they increase the potential for a severe and fatal NH4 toxicity damage.
... Various flavonoids are also found in Cannabis and may give the plant some of its exclusive medicinal benefits (Russo et al., 2003). Flavonoids are hydroxylated polyphenolic compounds consisting of two benzene rings linked via a heterocyclic pyran ring (Bautista et al., 2021). ...
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Medical Cannabis and its major cannabinoids (−)-trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex.
... There are also eighteen different chemical classes of substances, such as nitrogen compounds, amino acids, hydrocarbons, carbohydrates, terpenes, organics, and fatty acids [8,10]. The most important active compounds in cannabis are the psychoactive cannabinoid [11,12] delta-9-tetrahydrocannabinol (THC) [13,14], due to its lipophilic structure, enabling it to cross the blood-brain barrier, and nonpsychoactive cannabidiol (CBD) [15,16] (Figure 1). ...
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Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.
Nowadays, oral oil extracts of Cannabis represent the most relevant galenic plant-derived formulations employed in clinics. Nevertheless, the low and variable Δ9-tetrahydrocannabinol (THC) oral bioavailability due to hepatic first-pass metabolism and low solubility in biological fluids makes Cannabis pharmacological response highly unpredictable. In this scenario, new formulation strategies appear crucial to improve cannabinoids bioavailability and stability, administration comfort and patient compliance. Here, we present a nanoemulsion (NE) for the buccal administration of olive oil extract from a Cannabis sativa L. variety (Bedrocan®). A preliminary study was carried out on olive oil-based NE to identify the optimal formulation conditions to achieve a stable system. The Bedrocan®-loaded NE were then prepared and characterized for size, polydispersity index, stability upon delivery by the common buccal nebulizers. THC content and release in simulated buccal fluids and permeation studies across porcine buccal mucosa. The Bedrocan® NEs ensured THC stability and solubility in the buccal medium as compared with the Cannabis oil extract. Furthermore, the nanoemulsification process led to a THC diffusion and absorption on buccal mucosa 20-folds and 2-folds higher than olive oil extract, respectively. Overall, the results suggest that Bedrocan® NE represents a novel formulation strategy for the buccal administration of Cannabis extracts that can overcome the limits associated with conventional oily formulations.
Hemp is a crop that has been used since ancient times for its medicinal and textile applications, which is experiencing a resurgence today. This growing interest is due to the fact that hemp is a crop with multipurpose applications: a source of cellulosic and woody fibers, produces oil-rich seeds, is a raw material for phytochemicals and is driven by consumer demand for more natural and sustainable products. Residues recovered during the harvesting and processing of hemp fibers and/or seeds can be utilized to obtain an essential oil rich in phytochemicals with multiple applications. We review the recent progress and developments in hemp essential oil as a complex mixture of bioactive compounds with antiinflammatory, antibacterial, insecticidal and therapeutic properties, and whose exploitation can add value to hemp cultivation. Essential oils are widely used globally, and their use is constantly increasing. This could boost the utilization and market value of hemp essential oil.
Objective: We sought to determine whether acute delta 9-tetrahyrdrocannabidol (THC) administration would facilitate fear extinction in young occasional cannabis users, given that animal models indicate THC facilitates extinction learning, and recent studies indicate THC administration may also enhance threat memory extinction in humans. Methods: On each of the 2 days, 24+ hour THC-deprived participants were conditioned to fear visual stimuli in a delay conditioning and extinction paradigm. Both CS+ and CS- were faces of negative emotional valence, with the CS+ paired with mild electric shock. Throughout both conditioning and extinction paradigms, EEG was measured to quantify event-related potentials for these learning processes. Following conditioning, individuals, in a randomized and counter-balanced order, smoked either an active THC cigarette (26.25 mg/2.7% THC) or a placebo marijuana cigarette (0.002% THC) on 1 day and the opposite cigarette on the second day. After smoking, CS+ and CS- were presented without shock, resulting in extinction of conditioned fear. Results: Relative to placebo, THC facilitated extinction of the conditioned response to the CS+, as reflected by reductions in late positive potential amplitude during extinction learning. Conclusions: The results indicate that acute THC administration may facilitate extinction of the conditioned fear response in humans.
Introduction: Cannabis' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to identify the available evidence and knowledge gaps within the existing literature on cannabis product exposures as a potential cause of seizures in humans. Methods: A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews guidelines. The PubMed and Scopus databases were searched over a 20-year period from the date of the database query (12/21/2020). Inclusion criteria were (1) English language original research articles, (2) inclusion of human subjects, and (3) either investigation of seizures as a part of recreational cannabinoid use OR of exogenous cannabinoids as a cause of seizures. Results: A total of 3104 unique articles were screened, of which 68 underwent full-text review, and 13 met inclusion/exclusion criteria. Ten of 11 studies evaluating acute cannabis exposures reported a higher seizure incidence than would be expected based on the prevalence of epilepsy in the general and pediatric populations (range 0.7-1.2% and 0.3-0.5% respectively). The remaining two studies demonstrated increased seizure frequency and/or seizure-related hospitalization in recreational cannabis users and those with cannabis use disorder. Conclusions: This scoping review demonstrates that a body of literature describing seizures in the setting of cannabis exposure exists, but it has several limitations. Ten identified studies showed a higher than expected incidence of seizures in populations exposed to cannabis products. Based on the Bradford Hill criteria, delta-9 tetrahydrocannabinol (THC) may be the causative xenobiotic for this phenomenon.
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Cannabis is now emerging from a period of prohibition and being revisited as a potential source of treatments for conditions ill served by synthetic substances. Previous research focussed primarily on effects produced by synthetic cannabinoids such as THC, or cannabis of unknown cannabinoid content. Chemovars of cannabis characterized by high content of specific cannabinoids (primarily, but not only THC and CBD) have been developed. Clinical research using defined extracts from these chemovars is now underway in the UK.Many diseases are multifactorial; a variety of receptors need to be targeted to produce a therapeutic effect. A defined botanical may better achieve this than a single synthetic compound as the components can act synergistically. A new generation of cannabis based medicinal products takes advantage of increasing understanding of the mode of action of cannabinoids, evidence-based research on clinical uses and new technology for realization of products, in anti-diversionary presentations.
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. A central tenet underlying the use of botanical remedies is that herbs contain many active ingredients. Primary active ingredients may be enhanced by secondary compounds, which act in beneficial syn-ergy. Other herbal constituents may mitigate the side effects of dominant active ingredients. We reviewed the literature concerning medical can-nabis and its primary active ingredient, ∆ 9 -tetrahydrocannabinol (THC). Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC. Other cannabinoid and non-cannabinoid compounds in herbal cannabis or its extracts may reduce THC-induced anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activ-ity. [Article copies available for a fee from The Haworth Document Delivery Service: and: Cannabis Therapeutics in HIV/AIDS (ed: Ethan Russo) The Haworth Integrative Healing Press, an imprint of The Haworth Press, Inc., 2001, pp. 103-132. Single or multiple copies of this arti-cle are available for a fee from The Haworth Document Delivery Service [1-800-342-9678, 9:00 a.m. -5:00 p.m. (EST). E-mail address:].
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The toxicokinetics of alpha-pinene were studied in human volunteers exposed by inhalation (2 h, 50 W) in an exposure chamber on four occasions. The exposures were about 10, 225, and 450 mg/m3 (+)-alpha-pinene and 450 mg/m3 (-)-alpha-pinene. The relative pulmonary uptake was about 60% for the higher exposures, and total uptake increased linearly with increasing exposure. The total blood clearance was high, about After the exposure was terminated, less than 0.001% of the total uptake was eliminated unchanged in the urine and about 8% in exhaled air. A long half-time in poorly perfused tissues indicates a high affinity to adipose tissues. There was a statistically significant exposure-response relationship among five subjects who experienced irritation. Short-time exposure to alpha-pinene did not give rise to acute changes in lung function 20 min after the exposure.
The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by ?9-TCH in normal volunteers, and whether this effect occurs by a general block of the action of ?9-TCH or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg ?9-TCH, 1 mg/kg CBD, a mixture containing 0.5 mg/kg ?9-TCH and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by ?9-TCH, however this effect also extended to marihuanalike effects and to other subjective alterations induced by ?9-TCH. This antagonism does not appear to be caused by a general block of ?9-TCH effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of ?9-TCH.
Fragrance compounds and essential oils with sedative effects influence the motility of mice in inhalation studies under standardized conditions. A significant drop in the motility of mice was registered following exposure to these fragrances. The same results were achieved when the mice were artificially induced into overagitation by intraperitoneal application of caffeine and subsequently subjected to inhalation of fragrance compounds and essential oils. These results proved the sedative effects of these fragrants via inhalative exposure in low concentrations. Blood samples were taken from the mice after a 1-h inhalation period. Chromatographic and spectroscopic methods were used to detect and characterize the actual effective compounds after solid-phase extraction. Serum concentrations of 42 different substances, including fragrance compounds, were found in low ranges (ng/mL serum). The results contribute to the correct interpretation of the term aromatherapy (i.e., a stimulating or sedative effect on the behaviour of individuals only upon inhalation of fragrance compounds).
Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist Δ9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both a-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
Oral administration of an infusion of lemongrass (Cymbopogon citratus) fresh leaves to rats produced a dose-dependent analgesia for the hyperalgesia induced by subplantar injections of either carrageenin or prostaglandin E2, but did not affect that induced by dibutyryl cyclic AMP. These results indicate a peripheral site of action which was confirmed with the essential oil obtained by steam distillation of the leaves. Silica gel column fractionation of the essential oil allowed the identification of myrcene as the major analgesic component in the oil. Identification of the components was made by thin-layer chromatography and checked by mass spectrometry. The peripheral analgesic effect of myrcene was confirmed by testing a standard commercial preparation on the hyperalgesia induced by prostaglandin in the rat paw test and upon the contortions induced by intraperitoneal injections of iloprost in mice. In contrast to the central analgesic effect of morphine, myrcene did not cause tolerance on repeated injection in rats. This analgesic activity supports the use of lemongrass tea as a "sedative" in folk medicine. Terpenes such as myrcene may constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs.
Myrcene, a monoterpene isolated from lemon grass oil (Cymbopogon citratus) has been investigated for antinociception in mice by a low temperature (51.5 +/- 0.5 degrees C) hot plate method and by the acetic acid-induced writhing test. Significant inhibition of nociception was seen in the tests with myrcene at doses of 10 and 20 mg kg-1 (i.p.) or at 20 and 40 mg kg-1 (s.c.), respectively. The antinociceptive effect was significantly antagonized by naloxone (1 mg kg-1) or yohimbine (2 mg kg-1). The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated release of endogenous opioids.
Marijuana cigarettes of three different potencies (0.0%, 1.4% and 2.7% delta-9-tetrahydrocannabinol (THC) content) provided by the National Institute on Drug Abuse (NIDA) were compared on a variety of characteristics, including physical appearance, weight, burn rate, and deliveries of total particulate matter and carbon monoxide. Significant differences between the different potency cigarettes were obtained on most measures. These differences could be relevant to the design and interpretation of pharmacologic/toxicologic and behavioral studies conducted with these cigarettes. The possible basis for these observed differences, methods for minimizing some of them, and other potential problems related to the use of NIDA marijuana cigarettes are discussed.