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Bhanga (Cannabis sativa L.) as an activity potentiator in Ayurvedic classics and Indian alchemy (Rasashastra): A critical review
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Bhavana (impregnation) and Swedana (boiling) are the processes used in Ayurvedic pharmacy for preparation of formulations containing the drugs of metallic, mineral and poisonous origin to make them safe and potent for internal administration. Drugs of herbal origins are primely used for the Bhavana process. Bhanga (Cannabis sativa Linn.) a drug with great medicinal potency has been highlighted for its Deepana (digestive stimulant), Pachana (digestive), Ruchya (Taste promoter), Madakari (intoxicant), Vyavayi (short acting), Grahi (withholds secretions), Medhya (memory booster), Rasayana (adapto-immuno-neuro-endocrino-modulator) activities were used as a processing media in many formulations. In 19th century, it is included in narcotic group of plants and its use, as a drug, has been restricted. In 21st century again, the drug is gaining attraction from scientific communities due to its wide pharmacological properties. However, there is no collective information available at a glance regarding the use of Bhanga in various processing techniques of classical formulations. Hence, it is the need of the time to present the comprehensive information on cannabis, as quoted in classical texts with probable research co-relation, so as to bring the drug again in to limelight. The present review aims to compile all the information about the use of cannabis as an activity potentiator so that it can be further practically utilized in pharmaceutics and clinics with legal permissions. A thorough review, from available 41 Rasagranthas (text related to Indian alchemy) and 26 classical texts was carried out to compile the information about formulations where Bhanga is used as process media. The review shows that; Bhanga has been used, as a pharmaceutical processing agent, in 157 formulations being indicated in 40 different disease conditions. Among them, in 154 formulations, it is used as Bhavana media and in 3 formulations as a Swedana media. The present observation could help the future researchers to explore the drug for therapeutic utilities
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... The media used in these methods change the qualities of the principal ingredients, the major being metal-based compounds. A thorough review has documented that Bhanga has been used for trituration media, i.e., Bhavana (impregnation) in 154 formulations and for Swedana Dravya (boiling media) in three formulations (Tavhare and Acharya 2016). Rasayogasagara has quoted the highest formulations containing Bhanga as Bhavana (impregnation) media, followed by Bruhatrasarajasundara and Rasajalanidhi. ...
... Bhanga has been used in Bhavana (impregnation) form in formulations for forty disease conditions. Maximum formulations have been advocated in the management of Jwara (~pyrexia) followed by Grahani (malabsorption) and Atisara (Diarrhea) (Tavhare and Acharya 2016). Thus, a purified form of Bhanga is therapeutically valuable for gastrointestinal (GI) diseases. ...
Ayurveda has delineated a unique classification entitled ‘Upavisha varga’ comprising of certain semi-poisonous medicinal plants. Bhanga (Cannabis) is one amongst them in this category depicting its narcotic nature from Sanskrit synonyms. Bhanga has been in use since the Vedic age under the controversial plant of Soma that had special importance due to its mystical effects on the brain. All the texts of Ayurveda have described Bhanga in detail of its pharmacological properties, indications, various dosage forms, doses, pharmacovigilance aspects, and its extensive use in Indian Alchemy. The following review throws light on the occurrence and usage of Bhanga in excerpts from classical texts of Ayurveda from a pharmacological and pharmaceutical point of view thus, providing a rationale for its safe medical usage.KeywordsAyurveda
Bhanga
CannabisClassicalEvidenceReviewUpavishaVijaya
... [48] The leaves of Gunja (Abrus precatorius) are used to treat cough, fever, and cold. [49,50] Sarpapitta (snake bile) is used in the preparation of 2 of these formulations, they are Anandarasa and Soochimukharasa. ...
Vatsanabha is Vishavarga dravya mentioned in many of the Ayurveda Samhitas, which is commonly used in Ayurvedic medicinal preparations. It has a property of Jwarahara, Amaghna, Swedajana which is very useful in Jwara cases. The drugs like Parada, Gandhaka, Hingula along with Vatsanabha shows fast action on Jwara. In Ayurveda there are many formulations mentioned with Jwarahara properties. In this article we are studying about 17 Jwarahara Gutika yogas containing Vatsanabha which are mentioned in Sahasrayogam. Purpose of this study is to analyse these Yoga in the aspect of their ingredients, Bhavana dravya, Anupana, Sevana vidhi, and their role in management of Jwara. When we analysing each and every ingredients on these Yogas there are certain similarities in ingredients, Bhavana dravya, Anupana of these medicines. Most of these ingredients have Deepana Pachana karma, Katu Thikta rasa, Ushna veerya, Katu vipaka etc which are beneficial for Samprapti vighatana of Jwara. As Sahasrayogam is a compilation of popular formulations which are commonly used by ancient physicians of Kerala, it is assumed that all of this Yoga were once in practice. These formulations are to be kept in tablet form which is very convenient for their administration, palatability etc. But very few of them are available in market. In this current scenario of Covid pandemic Ayurveda field should rethink about these potent medicines of Jwara for the well being of our community, and further study and clinical trial also needed to know their action on Jwara.
... Cannabis is well reported for aphrodisiac, adaptogenic and immune-modular actions. [61] It helps in nourishing and improvement of body tissue and immunity. Cannabis being appetizer, digestive, tonic, antipyretic, analgesic, aphrodisiac, adaptogen, quick acting, memory tonic etc., helps in skirmishing pain along with associated cluster of symptoms which eventually helps in improving QOL in patients. ...
Introduction: Pain is a common and complex symptom of cancer having physical, social, spiritual and psychological aspects. Approximately
70%–80% of cancer patients experiences pain, as reported in India. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis)
for the management of pain but no research yet carried out on its clinical effectiveness. Objective: To assess the analgesic potential of JalaPrakshalana (Water-wash) processed Cannabis sativa L. leaves powder in cancer patients with deprived quality of life (QOL) through openlabel
single arm clinical trial. Materials and Methods: Waterwash processed Cannabis leaves powder filled in capsule, was administered in 24
cancer patients with deprived QOL presenting complaints of pain, anxiety or depression; for a period of 4 weeks; in a dose of 250 mg thrice
a day; along with 50 ml of cow’s milk and 4 g of crystal sugar. Primary outcome i.e. pain was measured by Wong-Bakers FACES Pain Scale
(FACES), Objective Pain Assessment (OPA) scale and Neuropathic Pain Scale (NPS). Secondary outcome namely anxiety was quantified by
Hospital Anxiety and Depression Scale (HADS), QOL by FACT-G scale, performance score by Eastern Cooperative Oncology Group (ECOG)
and Karnofsky score. Results: Significant reduction in pain was found on FACES Pain Scale (P < 0.05), OPA (P < 0.05), NPS (P <
0.001), HADS (P < 0.001), FACT-G scale (P < 0.001), performance status score like ECOG (P < 0.05) and Karnofsky score (P <
0.01). Conclusion: Jalaprakshalana Shodhita Bhanga powder in a dose of 250 mg thrice per day; relieves cancerinduced pain,
anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period
... Use of Bhanga, as a levigating media, in the treatment of 40 disease conditions has been reported. [49] It is found that; maximum formulations i.e. 36 [50] Bhanga, being Vyavayi [51] in action, brings fast acting nature to formulation. This is due to its Tikta Rasa which has Aakasha Vayu Mahabhuta (element) composition, Ushna Veerya, Laghu and Teekshna Guna. ...
Bhanga (Cannabis sativa L.),Cannabinaceae family, an annual herbaceous plant, has been used since millennia as a source of medicine, industrial fibre, seed oil, food,recreation, religious and spiritual moods. This fast-growing plant has recently seen a resurgence of interest because of its wide applications. Ayurveda, the science of life, describing many of the formulation about the pharmaco-clinical application of Bhanga but many of these formulations are not in practice today. Indeed; it is a treasure trove of multi-variant Guna (qualities) and Karma (actions), making it a broad spectrum drug. In this review, the rich spectrum of cannabis is being discussed by putting a special emphasis on the formulations containing cannabis either as a major or a minor ingredient. Available 41 Rasagranthas and 26 Chikitsagrantha and other Ayurvedic treatises were referred with respect to Bhanga’s Adhikara (main indication), Kalpana (dosage forms), Anupana (vehicle), Aushadha Sevana Kala (time and period of administration),Pathya- Apathya(do’s and dont’s),Prayojyanaga (parts used), Karma (action), specific uses and instructions of the formulations. It is observed that, there are 210 formulations which contain Bhanga, out of which 193 are recommended for internal administration and 17 for external applications. Among the formulations indicated for internal administration, 102 contain Bhanga as one of the major ingredient, whereas in 91 formulations, it’s a minor ingredient. Nine formulations of external application are having Bhanga as major ingredient and 8 as minor ingredient.The review represents formulations being indicatedof 45 differentRoga- Adhikara, 22 Kalpana,18 Pathya- Apathya, five different parts used, 49 Karma (action) and few benefits and instruction to be followed during administration of formulations containing Bhanga.
Keywords: Ayurveda, Bhanga, Cannabis sativa, Kalpana, Anupana, Matra, Shodhana
... There is no classical evidence that, the formulations containing Bhanga either as an ingredient or as a levigating media can be given in pregnancy. [64] However, Animal studies reports that cannabis exposure during pregnancy may alter the normal processes and trajectories of brain development. [65] Long-term effects of marijuana consumption on prenatal exposure to humans is yet to be explored. ...
Bhanga (Cannabis sativa L.),Cannabinaceae family, an annual herbaceous plant, has been used since millennia as a source of medicine, industrial fibre, seed oil, food,recreation, religious and spiritual moods. This fast-growing plant has recently seen a resurgence of interest because of its wide applications. Ayurveda, the science of life, describing many of the formulation about the pharmaco-clinical application of Bhanga but many of these formulations are not in practice today. Indeed; it is a treasure trove of multi-variant Guna (qualities) and Karma (actions), making it a broad spectrum drug. In this review, the rich spectrum of cannabis is being discussed by putting a special emphasis on the formulations containing cannabis either as a major or a minor ingredient. Available 41 Rasagranthas and 26 Chikitsagrantha and other Ayurvedic treatises were referred with respect to Bhanga's Adhikara (main indication), Kalpana (dosage forms), Anupana (vehicle), Aushadha Sevana Kala (time and period of administration),Pathya-Apathya(do's and dont's),Prayojyanaga (parts used), Karma (action), specific uses and instructions of the formulations. It is observed that, there are 210 formulations which contain Bhanga, out of which 193 are recommended for internal administration and 17 for external applications. Among the formulations indicated for internal administration, 102 contain Bhanga as one of the major ingredient, whereas in 91 formulations, it's a minor ingredient. Nine formulations of external application are having Bhanga as major ingredient and 8 as minor ingredient.The review represents formulations being indicatedof 45 differentRoga-Adhikara, 22 Kalpana,18 Pathya-Apathya, five different parts used, 49 Karma (action) and few benefits and instruction to be followed during administration of formulations containing Bhanga.
This book series invites all the Specialists, Professors, Doctors, Scientists, Academicians, Healthcare professionals, Nurses, Students, Researchers, Business Delegates, and Industrialists across the globe to publish their insights and convey recent developments in the field of Nursing, Pharmaceutical Research and Innovations in Pharma Industry. Book series on Pharmacy and Nursing covers research work in a set of clinical sciences and medicine.
Ayurveda is the world's oldest and most complete spiritual teachings, as well as the "oldest medicinal system" known to man. Ayurvedic treatments along with natural substances do not have any usual side effects as contemporary drugs. The cannabis plant has been used as a medicine for thousands of years to treat various illnesses including gastrointestinal disorders. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-known and researched phyto cannabinoids, with impressive therapeutic properties for a variety of neurological, gastrointestinal, ophthalmic, and skin problems. Cannabis and cannabinoids are beneficial in healing the sign and symptoms of several gastrointestinal diseases, according to research, in part because they interact with the digestive tracts endogenous cannabinoid receptors. This could help in relaxing pain and cramps, reducing discomfort, and improving motility. Many Indian classical formulations were found cannabis is used processing agent in pharmaceuticals. For the treatment of GI issues, there are some popular cannabis-based ayurveda or herbal formulations on the market. CBD levels are frequently higher in medical marijuana, while THC levels are lower. For certain people, the therapeutic CBD is desirable for medicinal purposes, but the psychoactive THC may be needless and undesired. There are numbers of traditional cannabis formulations on the market that lack standardised quality control parameters and methods of evaluation.So, there is a need to develop a standardization technique with special reference to CBD and THC content to include this system of medicine in the main stream of health science. Standardization of popular Ayurvedic or herbal formulations is essential in order to assess the quality, safety, efficacy of that.
Background: Cannabis (Bhanga) has been extensively explored in research for therapeutic benefits. Out of 80+ phyto-cannabinoid detected till date; out of which Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN) are therapeutically important. Psychotropic concern about cannabis is a majorly attributed to THC presence. For reducing intoxicant effect, Ayurveda recommends processing (Shodhana) of cannabis. Objectives: To evaluate impact of cannabis leaves processing techniques through pharmacognosy, photochemistry and chromatography. Material and methods: Four different processing methods; namely water-immersion (Jala-nimajjana) (JN), water-wash (Jala-prakshalana) (JP), boiling in cow’s milk (Godugdha-Swedana) (GS) and boiling in decoction of Acacia arabica (Babbul twak Kwatha-Swedana) (BKS) were performed as mentioned in Ayurveda classics. Water and ethanol extract of respective sample and processing media were prepared. Processed samples were evaluated for physicochemical, qualitative and chromatographic studies (HPTLC) and comparative evaluation was done against markers THC, CBD and CBN. Results: Processed samples showed variation in physico-chemical parameters. Functional groups like carbohydrates, phenols and steroids retained after processing in all samples. Additionally; protein and tannin groups were found in samples processed by GS and BKS method. Processing of cannabis reduced THC, CBD and CBN from samples and which transferred to media as quantified through HPTLC. In GS method, no maker visualized through HPTLC. This may be due to changes in nature of molecules caused by boiling. Reduction of THC found highest in JP (31%) followed by JN (18%) and BKS (16%) method. Conclusion: Processing showed changes in physicochemical parameters of cannabis leaves and reduces its THC content;thus; reducing its intoxicant effect without altering presence of functional group.
Bhanga (Indian hemp, pot, dope) is a Neurotoxic cerebral deliriant poison, obtained from Cannabis sativa. It is dioecious flowering herb, in which female plant contains more Cannabinoid than male. It produces a gummy, amorphous resin, cannabinone. It is enclosed under Narcotic drugs and psychotropic substances (NDPS) Act 1985. The various forms of Cannabis sativa are bhanga (sidhi, patti or sabji), majun, ganja and charas. It has many therapeutic uses; it acts as sedative and so many misuse of bhanga reported since ancient time. It is one of the most commonly used illicit drug since ages. It has been used for the treatment of several diseases and disorders by communities from all over the world. Studies shows that Cannabis sativa is having numerous pharmacological actions on human and animal trials. It is regulated by law in our country. Its management has been mentioned in various samhita and modern science.
Bhanga (Cannabis) has been reported with numerous therapeutic, traditional, commercial, and sacred uses in India and across the globe. Its uses are deeply rooted in the cultural, social, and economic lives of the people. The inclusion of Cannabis under ‘Scheduled E1’ drugs in India restricts its use. However, being a crop of economic and medicinal importance, the pharmaceutical and various other
sectors are showing much interest in the plant. The present review article delineates traditional, culinary, cosmetic, ritual, social, spiritual, recreational, economic, and therapeutic uses of Cannabis. The review illustrates various uses of Cannabis across the globe; noted from articles, publications, and books providing description of
various parts, viz. leaves and seeds (Bhanga), flowering and fruiting tops (Ganja), resin (Charas), extract, tincture, and whole plant, stalks (Fibers). The review may be helpful to researchers, clinicians, and pharmaceutical companies to carry out further research for developing cost-effective healthcare options.
Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies characterizing (1) SCs acute effects, (2) withdrawal upon cessation of use, and (3) effective treatment strategies for SC use disorder are urgently needed.
Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions. There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way. What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics. In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals.
Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration-time curves for either morphine or oxycodone after exposure to cannabis. Pain was significantly decreased (average 27%, 95% confidence interval (CI) 9, 46) after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects.
The present study was designed to explore the relationship between the cannabinoid and opioid receptors in animal models of opioid-induced reinforcement. The acute administration of SR141716A, a selective central cannabinoid CB1 receptor antagonist, blocked heroin self-administration in rats, as well as morphine-induced place preference and morphine self-administration in mice. Morphine-dependent animals injected with SR141716A exhibited a partial opiate-like withdrawal syndrome that had limited consequences on operant responses for food and induced place aversion. These effects were associated with morphine-induced changes in the expression of CB1 receptor mRNA in specific nuclei of the reward circuit, including dorsal caudate putamen, nucleus accumbens, and septum. Additionally, the opioid antagonist naloxone precipitated a mild cannabinoid-like withdrawal syndrome in cannabinoid-dependent rats and blocked cannabinoid self-administration in mice. Neither SR141716A nor naloxone produced any intrinsic effect on these behavioral models. The present results show the existence of a cross-interaction between opioid and cannabinoid systems in behavioral responses related to addiction and open new strategies for the treatment of opiate dependence.
Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several countries. The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects.
Cannabis has been used for centuries in the medicinal treatment of gastrointestinal disorders. Endogenous cannabinimimetic substances such as 2-arachidonylglycerol have been isolated from gut homogenates and CB1-cannabinoid binding sites have been identified in small intestine. In this study, CB1-cannabinoid receptors (CB1-R) were immunohistochemically localized within the enteric nervous system of the pig, an omnivorous species whose digestive tract is functionally similar to humans. Two anti-CB1-R antisera, raised against N-terminal epitopes in the human CB1-R, were employed to localize receptor immunoreactivity by secondary immunofluorescence. CB1-R immunoreactivity was observed in the myenteric and submucosal ganglionated plexuses of porcine ileum and colon. In the ileum, all CB1-R-immunoreactive neurons coexpressed immunoreactivity to the cholinergic marker, choline acetyltransferase (ChAT). CB1-R/ChAT-immunoreactive neurons appeared to be in close apposition to ileal Peyer's patches, submucosal blood vessels, and intestinal crypts. In the distal colon, CB1-R-immunoreactive neurons also expressed immunoreactivity to ChAT, albeit less frequently than in ileum. Immunoreactivity to vasoactive intestinal peptide or nitric oxide synthase was not colocalized in ileal or colonic CB1-R-immunoreactive neurons. These studies indicate that CB1-R are present in cholinergic neurons in the porcine enteric nervous system. The potential roles of these receptors in intestinal motility and epithelial transport, host defense and visceral pain transmission are discussed.
Cannabis (marijuana) is the most widely used illicit drug globally. Given the prevalence of nonprescription illicit drug abuse, there is a growing interest in the study of its potential effects on male sexual health. In this review, we discuss the effects of cannabis on male sexual health.
In this review, we discuss the effects of cannabis on male sexual health. METHODS AND MAIN OUTCOME MEASURE: Critical review of scientific literature examining the impact of cannabis use on male sexual health.
Studies examining the effects of cannabis use on male sexual function have been limited in both quality and quantity. Most results of these studies are conflicting and contradictory. While some did outline the beneficial effects of cannabis in enhancing erectile function, others did not. However, recent animal and in vitro studies have identified potential links between cannabis and sexual health. It appears that cannabis may actually have peripheral antagonizing effects on erectile function by stimulating specific receptors in the cavernous tissue.
Given the prevalence of cannabis use, and the potential relationships between use and the development of potentially hazardous effects on male sexual function, we encourage renewed use of research resources to determine in-depth mechanistic knowledge, and new clinically oriented studies examining the effect of cannabis on male sexual function.
Activation of cannabinoid CB(1) receptors inhibits gastrointestinal motility, propulsion, and transit, whereas selective antagonism of these receptors has the opposite effects, suggesting the presence of endocannabinoid tone. Supporting evidence for presynaptic CB(1) receptors on myenteric neurons has been found in vitro. In this study, selective CB(1) receptor antibodies and neuronal markers were used to identify and characterise myenteric neurons expressing cannabinoid receptors. Whole mounts of rat and guinea pig myenteric preparations were dually labelled with antibodies against the CB(1) receptor and choline acetyltransferase, neurofilament proteins, calbindin, calretinin, synapsin I, microtubule-associated protein-2, calcitonin gene-related peptide, or substance P. The pattern of CB(1) receptor labelling and the neurochemical classification of CB(1) receptor-positive cells were markedly influenced by the species and fixation procedure. Virtually all choline acetyltransferase-immunoreactive myenteric neurons expressed CB(1) receptors in ganglia from both species. Subpopulations of neurons identified with calbindin, calretinin, and microtubule-associated protein-2 did not express CB(1) receptors. A few calcitonin gene-related peptide- and substance P-positive somata coexpressed CB(1) receptor immunoreactivity but showed little colocalisation on individual fibres. There was a close association between CB(1) receptor immunoreactivity and fibres labelled for synaptic protein, suggesting a role in the modulation of transmitter release. Functional responses to cannabinoids in the presence of hexamethonium suggest further that CB(1) receptors occur on excitatory motoneurons. In conclusion, CB(1) receptors are expressed on a variety of cholinergic sensory, interneuronal, and motor neurons in myenteric ganglia.
Recent work in the field of gastrointestinal pharmacology of cannabinoids has focused on enteric endocannabinoid and endovanilloid systems and their modulation in pathophysiological conditions. CB(1) receptor immunoreactivity was detected on enteric cholinergic neurones and vasoactive intestinal peptide-containing submucosal ganglion cells, on discrete nuclei of the dorsovagal complex (involved in emesis) and on central and peripheral vagal terminals, thus controlling gastroesophageal reflux and gastrointestinal motility. CB(1) receptor activation by endocannabinoids inhibited induced fluid secretion and inflammation in animal models and reduced proliferation of cultured colorectal cancer cells. Endocannabinoids also activate cannabinoid CB(2) and vanilloid VR1 receptors in certain inflammatory states. Thus endocannabinoid metabolism could provide a useful therapeutic target for many gastrointestinal disorders.