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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of delta9-tetrahydrocannabinol (delta9-THC) and cannabinol (CBN) was studied in man. Five male volunteers were given placebo, 50 mg CBN, 25 mg delta9-THC, 12.5 mg delta9-THC + 25 mg CBN, and 25 mg delta9-THC + 50 mg CBN (orally). Administrations were spaced 1 week apart. With physiological measures, delta9-THC produced an increase in heart rate while CBN did not. When combined, no change of the delta9-THC effect occurred. No changes occurred on the electrocardiogram, blood pressure, or body temperature. With psychophysical measures no changes occurred in pain thresholds or skin sensitivity as a function of drug treatment. In time estimates of the passage of 1 minute, delta9-THC alone produced underestimates of the passage of 1 minute and CBN alone had no effect. In combination the two drugs had a tendency to produce significant overestimates and underestimates of the passage of 1 minute. On a 66-item adjective-pair drug reaction scale, the volunteers reported feeling drugged, drunk, dizzy, and drowsy under the delta9-THC condition, but not under the CBN condition. With combined drug treatment, volunteers reported feeling more drugged, drunk, dizzy, and drowsy than under the delta9-THC condition alone. None of the drug treatments produced significant changes on other items which included items on perception, emotion, cognition and sociability. It appears that CBN increases the effect of delta9-THC on some aspects of physiological and psychological processes, but that these effects are small and cannot account for the greater potency which has been reported when plant material is used.
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PMID:Effects of delta9-tetrahydrocannabinol and cannabinol in man. 122 32

Sixteen habitual marihuana users, selected for their good mental and physical health, were hospitalized for three months in the New York State Psychiatric Institute. During the first month, the subjects were drug free; during the second month, they smoked marihuana cigarettes provided by NIDA (2% THC, 20 mg per cigarette) at the rate of 3 to 12 a day. A modified Hardy-Wolff dolorimeter was used to present 20 thermal stimuli of 30-second duration in a random manner at nine different intensities. Subjects responded from a 14-category scale, and data were analyzed according to sensory decision theory analysis. During the third month, the subjects were again drug free. At the noxious thermal intensities, there was a decrease in the pain report criterion during the first two weeks of smoking. The pain enhancement effect was followed by return to the presmoking pain level during weeks 3 and 4 and in the postsmoking period, indicating that tolerance had developed. There was also an increase in pain discriminability during the four weeks of smoking which extended for one week after smoking. Tolerance developed to the pain report criterion but not to the thermal discriminability. This study suggests that marihuana may have hyperalgesic activity and probably enhances the perception of pain, in moderate smokers. In contrast, heavy smoking had little effect on discriminability and caused an increase in the pain report criterion.
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PMID:Effects of moderate and high doses of marihuana on thermal pain: a sensory decision theory analysis. 729 71

Cannabinoids, such as Delta9-THC, are capable of inhibiting nociception, i.e., pain transmission, at least in part, by interacting with spinal Gi/Go-coupled cannabinoid receptors. What is not known, however, is the antinociceptive role of endogenous spinal cannabinoids. If endogenous cannabinoids modulate basal nociceptive thresholds, then alterations in this system could be involved in the etiology of certain pain states. In this report we provide evidence for tonic modulation of basal thermal nociceptive thresholds by the spinal cannabinoid system. Administration of oligonucleotides directed against CB1 cannabinoid receptor mRNA significantly reduced spinal cannabinoid binding sites and produced significant hyperalgesia when compared with a randomer oligonucleotide control. A second method used to reduce activity of the spinal cannabinoid receptor was intrathecal administration of the cannabinoid receptor antagonist SR 141716A. SR 141716A evoked thermal hyperalgesia with an ED50 of 0.0012 fmol. The SR 141716A-induced hyperalgesia was dose-dependently blocked by the administration of D-AP-5 or MK-801, two antagonists to the NMDA receptor. These results indicate that there is tonic activation of the spinal cannabinoid system under normal conditions. Furthermore, hypoactivity of the spinal cannabinoid system results in an NMDA-dependent hyperalgesia and thus may participate in the etiology of certain chronic pain states.
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PMID:Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia. 941 21

A broad range of therapeutic applications has been suggested for cannabis or its pharmacologically active compound (tetrahydrocannabinol; THC) in many publications. Psychotropic side effects and the anecdotal character of the research have limited the pharmacotherapeutic use of THC until now. Therefore, the Netherlands Health Council recently decided negatively on this matter. Besides several cannabinoid receptor subtypes present in the central nervous system and peripheral tissues endogenous cannabinoids have been detected. These endogenous cannabinoids appear to play an important role in signal transduction, which may be starting points for therapy regarding: cardiovascular diseases, multiple sclerosis and spinal cord disorders. cerebrovascular accident and brain trauma, neurodegenerative diseases, epilepsy, pain management, glaucoma, oncologic and aids-related disorders such as nausea, vomiting and appetite problems.
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PMID:[Therapeutic applications and biomedical effects of cannabinoids; pharmacological starting points]. 954 85

Cannabis, or Marijuana, has been used for centuries for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a headache remedy by the most prominent physicians of the age between 1874 and 1942, remaining part of the Western pharmacopoeia for this indication even into the mid-twentieth century. Current ethnobotanical and anecdotal references continue to refer to its efficacy for this malady, while biochemical studies of THC and anandamide have provided a scientific basis for such treatment. The author believes that controlled clinical trials of Cannabis in acute migraine treatment are warranted.
Pain 1998 May
PMID:Cannabis for migraine treatment: the once and future prescription? An historical and scientific review. 969 53

Perinatal delta9-tetrahydrocannabinol (delta9-THC) exposure in rats affects several behavioral responses, such as opiate self-administration behavior or pain sensitivity, that can be directly related to changes in opioidergic neurotransmission. In addition, we have recently reported that the administration of naloxone to animals perinatally exposed to delta9-THC produced withdrawal responses, that resemble those observed in opiate-dependent rats. The purpose of the present study was to examine the basal opioid activity in the brain of adult male and female rats that had been perinatally exposed to delta9-THC. To this aim, proenkephalin mRNA levels were measured, by using in situ hybridization histochemistry, in the caudate-putamen, nucleus accumbens, central amygdala and prefrontal cingulate cortex. The results showed a marked reduction in proenkephalin mRNA levels in the caudate-putamen of delta9-THC-exposed females as compared to oil-exposed females, whereas no changes were observed between delta9-THC- and oil-exposed males. There were no differences in proenkephalin mRNA levels in the nucleus accumbens, central amygdala and prefrontal cingulate cortex between males and females perinatally exposed to delta9-THC and their respective controls, although a certain trend to decrease was observed in delta9-THC-exposed females. In summary, perinatal exposure to delta9-THC exposure decreased proenkephalin gene expression in the caudate-putamen of adult rats, although this effect exhibited a marked sexual dimorphism since it was only seen in females. This result is in agreement with a previous observation from our laboratory that females, but not males, that had been perinatally exposed to delta9-THC, self-administered more morphine in adulthood. This suggests that low levels of proenkephalin mRNA may be used as a predictor of greater vulnerability to opiates.
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PMID:Perinatal delta9-tetrahydrocannabinol exposure reduces proenkephalin gene expression in the caudate-putamen of adult female rats. 973 4

The use of cannabis for the management of a wide range of painful disorders has been well documented in case reports throughout history. However, clinical evaluations of cannabis and its psychoactive constituent THC have not led to a consensus regarding their analgesic effectiveness. On the other hand, THC and its synthetic derivatives have been shown to be effective in most animal models of pain. These antinociceptive effects are mediated through cannabinoid receptors in the brain that in turn appear to interact with noradrenergic and kappa opioid systems in the spinal cord to modulate the perception of painful stimuli. The endogenous ligand, anandamide, is also an effective antinociceptive agent. The extent to which the endogenous cannabinoid system is involved in the modulation of pain is currently unknown.
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PMID:Cannabinoid transmission and pain perception. 997 77

The antinociceptive effects of various mu opioids given p.o. alone and in combination with Delta-9-tetrahydrocannabinol (Delta9-THC) were evaluated using the tail-flick test. Morphine preceded by Delta9-THC treatment (20 mg/kg) was significantly more potent than morphine alone, with an ED50 shift from 28.8 to 13.1 mg/kg. Codeine showed the greatest shift in ED50 value when administered after Delta9-THC (139.9 to 5.9 mg/kg). The dose-response curves for oxymorphone and hydromorphone were shifted 5- and 12.6-fold, respectively. Methadone was enhanced 4-fold, whereas its derivative, l-alpha-acetylmethadol, was enhanced 3-fold. The potency ratios after pretreatment with Delta9-THC for heroin and meperidine indicated significant enhancement (4.1 and 8.9, respectively). Pentazocine did not show a parallel shift in its dose-response curve with Delta9-THC. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of morphine p.o. and codeine p.o. The Delta9-THC-induced enhancement of morphine and codeine was also significantly decreased by naloxone administration. Naltrindole (2 mg/kg s.c.) did not affect morphine or codeine antinociception but did block the enhancement of these two opioids by Delta9-THC. No effect was seen when nor-binaltorphimine was administered 2 mg/kg s.c. before morphine or codeine. Furthermore, the enhancements of morphine and codeine were not blocked by nor-binaltorphimine. We find that many mu opioids are enhanced by an inactive dose of Delta9-THC p.o. The exact nature of this enhancement is unknown. We show evidence of involvement of mu and possibly delta opioid receptors as a portion of this signaling pathway that leads to a decrease in pain perception.
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PMID:Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. 1021 64

Although the active component of cannabis Delta9-THC was isolated by our group 35 years ago, until recently its mode of action remained obscure. In the last decade it was established that Delta9-THC acts through specific receptors - CB1 and CB2 - and mimics the physiological activity of endogenous cannabinoids of two types, the best known representatives being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG). THC is officially used against vomiting caused by cancer chemotherapy and for enhancing appetite, particularly in AIDS patients. Illegally, usually by smoking marijuana, it is used for ameliorating the symptoms of multiple sclerosis, against pain, and in a variety of other diseases. A synthetic cannabinoid, HU-211, is in advanced clinical tests against brain damage caused by closed head injury. It may prove to be valuable against stroke and other neurological diseases.
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PMID:Recent advantages in cannabinoid research. 1057 84

Cannabinoids and opioids are distinct drug classes historically used in combination to treat pain. Delta(9)-THC, an active constituent in marijuana, releases endogenous dynorphin A and leucine enkephalin in the production of analgesia. The endocannabinoid, anandamide (AEA), fails to release dynorphin A. The synthetic cannabinoid, CP55,940, releases dynorphin B. Neither AEA nor CP55,940 enhances morphine analgesia. The CB1 antagonist, SR141716A, differentially blocks Delta(9)-THC versus AEA. Tolerance to Delta(9)-THC, but not AEA, involves a decrease in the release of dynorphin A. Our preclinical studies indicate that Delta(9)-THC and morphine can be useful in low dose combination as an analgesic. Such is not observed with AEA or CP55,940. We hypothesize the existence of a new CB receptor differentially linked to endogenous opioid systems based upon data showing the stereoselectivity of endogenous opioid release. Such a receptor, due to the release of endogenous opioids, may have significant impact upon the clinical development of cannabinoid/opioid combinations for the treatment of a variety of types of pain in humans.
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PMID:Synergistic interactions of endogenous opioids and cannabinoid systems. 1061 10


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