Effects of intravenous tetrahydrocannabinol on experimental and surgical pain; Psychological correlates of the analgesic response

Raft, David; Gregg, John M.; Ghia, Jawahar N.; Harris, Louis S.

doi:10.1002/cpt197721126

Cited by 102 publications

(84 citation statements)

References 12 publications

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“…Altogether, these studies have M a n u s c r i p t 10 revealed a dose-dependent switch from reward to aversion, with low and high doses of cannabinoids inducing reward and aversion, respectively. An analogous phenomenon has been observed in human addicts, where low doses of THC or levonantradol are perceived as rewarding while higher doses as aversive (Noyes et al, 1975, Raft et al, 1977Laszlo et al, 1981).…”

supporting

confidence: 58%

Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: Fattore, L., Fadda, P., Spano, M.S., Pistis, M., Fratta, W., Neurobiological mechanisms of cannabinoid addiction, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 AbstractThe endocannabinoid system is implicated in the regulation of a variety of physiological processes, among which conditioning, motivation, habit forming, memory, learning, and cognition play pivotal roles in drug reinforcement and reward. In this article we will give a synopsis of last developments in research on cannabinoid actions on brain reward circuits coming from behavioral, neurochemical and electrophysiological studies. Central cannabinoid-induced effects as measured by animal models of addiction, in vivo cerebral microdialysis, in vitro and in vivo electrophysiological recording techniques, will be reviewed.Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids. Putative neurobiological mechanisms underlying these effects will be delineated.

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supporting

confidence: 58%

Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

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“…nonpainful sensations were affected but not the painful sensations [96]. Such findings could reflect that pain …”

Section: Non-opioid Analgesics In Experimental Painmentioning

confidence: 84%

“…However, the drug has shown a complex pattern of analgesia with a stronger effect on pain intensities below the pain detection threshold than on those above [96]. This pattern is opposite to that of classic analgesics such as opioids working mainly on suprathreshold intensities, and could reflect that delta-9-tetrahydrocannabinol works on the sensory-discriminative rather than affectivemotivational aspects of pain, which is in consensus of the findings of Wallace et al [94,96]. In hyperalgesic models pain from capsaicin, reflecting strong C-fibre activation, was decreased by delta-9-tetrahydrocannabinol…”

Section: Mechanistic Aspectsmentioning

confidence: 99%

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Staahl

Olesen

Arendt‐Nielsen

et al. 2009

Brit J Clinical Pharma

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AIMExperimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODSA literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTSNonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N-methyl-D-aspartate antagonists exemplified by ketamine generally needed strong, long-lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol attenuated pain in only a few models.

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“…In brief, there were contradictory findings in human studies on pain, with some research suggesting that THC relieved cancer pain about as well as 60 mg of codeine [56,57] and that levonantrodol, a synthetic THC-like cannabinoid was effective in post-operative and trauma pain [58]. On the other hand, Raft et al [59] found no effect of THC on the pain of tooth extraction, and Clark et al [60] found some suggestion that moderate to high doses of THC actually produced hyperalgesia.…”

Section: Results Of Earlier Research With Cannabis Thc and Its Syntmentioning

confidence: 99%

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Grant

Cahn

2005

Clinical Neuroscience Research

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The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.

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Effects of intravenous tetrahydrocannabinol on experimental and surgical pain; Psychological correlates of the analgesic response

Cited by 102 publications

References 12 publications

Neurobiological mechanisms of cannabinoid addiction

Neurobiological mechanisms of cannabinoid addiction

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

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