Tag Archives: antinociceptive

Restored Self: A Phenomenological Study of Pain Relief by Cannabis.

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Pain Medicine

“OBJECTIVE:

To explore the subjective experience of pain relief by cannabis.

RESULTS:

Three key themes that emerged from the analysis were explored: 1) the Sigh of Relief, describing the corporal sensation of using cannabis, including a sense of relaxation and reduction in pain; 2) the Return to Normality, describing the comprehensive effect of using cannabis, including an increased ability to sleep, focus, and function; and 3) the Side Effects of using cannabis.

CONCLUSIONS:

We propose the term Restored Self to conceptualize the effect of medical cannabis. Restored Self is the experience of regaining one’s sense of self, sense of normality, and sense of control over one’s life.”

 https://www.ncbi.nlm.nih.gov/pubmed/30215782
https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pny176/5095910?redirectedFrom=fulltext

ANTINOCICEPTIVE TOLERANCE TO NSAIDS PARTIALLY MEDIATED VIA ENDOCANNABINOIDS IN ANTERIOR CINGULATE CORTEX OF RATS.

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“Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems but also on the activation of mechanisms that control emotional processes in limbic brain areas.

Non-opioid, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics in the treatment of not-severe pain. We have recently shown that repeated doses result in tolerance to these drugs like opioids.

Here we investigated the central brain mechanisms of non-opioid induced antinociception in the non-acute pain models of rats, such as the ‘formalin test’ and a relation between administration of NSAIDs in the limbic brain area, – the anterior cingulated cortex (ACC), – and the endocannabinoid system.

The present data support the notion that endocannabinoids’ CB1 receptor contributes in part to antinociceptive effects of NSAIDs and probably involved in activation of the descending opioid modulatory system of pain.”

 https://www.ncbi.nlm.nih.gov/pubmed/30204109

Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole.

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“Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established.

Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system.

CONCLUSIONS:

These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.”

 https://www.ncbi.nlm.nih.gov/pubmed/30198932
https://insights.ovid.com/crossref?an=00000539-900000000-96532

Reinforcing effects of opioid/cannabinoid mixtures in rhesus monkeys responding under a food/drug choice procedure.

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Psychopharmacology

“Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ9-THC) enhance the antinociceptive potency of mu opioid receptor agonists such as morphine, indicating that opioid/cannabinoid mixtures might be effective for treating pain. However, such enhancement will be beneficial only if cannabinoids do not also enhance adverse effects of opioids, including those related to abuse.

In rhesus monkeys, cannabinoids fail to enhance and often decrease self-administration of the mu opioid receptor agonist heroin, suggesting that opioid/cannabinoid mixtures do not have greater reinforcing effects (abuse potential) compared with opioids alone. Previous studies on the self-administration of opioid/cannabinoid mixtures used single-response procedures, which do not easily differentiate changes in reinforcing effects from other effects (e.g., rate decreasing).

CONCLUSION:

Overall, these results extend previous studies to include choice behavior and show that cannabinoids do not substantially enhance the reinforcing effects of mu opioid receptor agonists.”

 https://www.ncbi.nlm.nih.gov/pubmed/29860612
https://link.springer.com/article/10.1007%2Fs00213-018-4932-6

Medication overuse headache following repeated morphine, but not [INCREMENT]9-tetrahydrocannabinol administration in the female rat.

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“The potential of [INCREMENT]-tetrahydrocannabinol (THC) as a treatment for migraine depends on antinociceptive efficacy with repeated administration.

Although morphine has good antinociceptive efficacy, repeated administration causes medication overuse headache (MOH) – a condition in which the intensity/frequency of migraine increases.

The present study compared the effect of repeated morphine or THC administration on the magnitude and duration of migraine-like pain induced by a microinjection of allyl isothiocyanate (AITC) onto the dura mater of female rats.

Acute administration of THC or morphine prevented AITC-induced depression of wheel running. This antinociception was maintained in rats treated repeatedly with THC, but not following repeated administration of morphine. Moreover, repeated morphine, but not THC administration, extended the duration of AITC-induced depression of wheel running.

These data indicate that tolerance and MOH develop rapidly to morphine administration. The lack of tolerance and MOH to THC indicates that THC may be an especially effective long-term treatment against migraine.”

 https://www.ncbi.nlm.nih.gov/pubmed/29462111
https://insights.ovid.com/crossref?an=00008877-900000000-99334

Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

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“Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use.
In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients.
In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses.
The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD.
We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.”  https://www.scirp.org/journal/PaperInformation.aspx?paperID=53912
“In conclusion, we recommend standardized plant extract of the Cannabis clone 202 for treatment of various inflammatory conditions.” https://file.scirp.org/Html/5-2500582_53912.htm

Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons.

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 Neuroscience

“Expression of cannabinoid 1 (CB1) and vanilloid 1 (VR1) receptor proteins was studied in adult, cultured rat dorsal root ganglion neurons. Immunostaining of CB1 receptors alone produced labelling in 57+/-2% of the cultured dorsal root ganglion neurons (n=3 cultures). The area of the labelled cells was between 200 and 800 microm(2) with an average of 527+/-68 microm(2). VR1 immunolabelling revealed immunopositivity in 42+/-6% of the total population of dorsal root ganglion neurons. Cells showing VR1-like immunopositivity had an area between 200 and 600 microm(2). The mean area of the VR1-like immunopositive neurons was 376+/-61 microm(2). Double immunostaining with antisera raised against the CB1 and VR1 receptor proteins, showed a high degree of co-expression between CB1 and VR1 receptors. An average of 82+/-3% of the CB1-like immunopositive cells also showed VR1-like immunoreactivity (n=3 cultures) while 98+/-2% of the VR1-like immunolabelled neurons showed CB1 receptor-like immunostaining (n=3 cultures). Our data suggests that nociceptive primary sensory neurons co-express CB1 and VR1 receptors to a very high degree. We propose that this may provide an anatomical basis for a powerful combination of VR1 mediated excitation and CB1-mediated inhibition of nociceptive responses at central and peripheral terminals of nociceptive primary afferents.”

https://www.ncbi.nlm.nih.gov/pubmed/11036202

https://www.sciencedirect.com/science/article/abs/pii/S0306452200003894

Emerging Role of (Endo)Cannabinoids in Migraine.

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“In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain.

Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors.

We explore the cannabinoid-mediated mechanisms in the frame of the Clinical Endocannabinoid Deficiency (CECD) hypothesis, which implies reduced tone of endocannabinoids in migraine patients. We further discuss the control of cortical excitability by cannabinoids via inhibition of cortical spreading depression (CSD) underlying the migraine aura.

Finally, we present our view on perspectives of Cannabis-derived (extracted or synthetized marijuana components) or novel endocannabinoid therapeutics in migraine treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/29740328

https://www.frontiersin.org/articles/10.3389/fphar.2018.00420/full

Antinociceptive Synergy between 9 -Tetrahydrocannabinol and Opioids after Oral Administration

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“Cannabinoids and opioids have been shown to possess several similar pharmacological effects, including analgesia

The analgesic effects of opioids, such as morphine and codeine, in mice are enhanced by oral administration of the cannabinoid 9 -tetrahydrocannabinol (9 -THC).

These findings suggest that the use of a low-dose combination of analgesics is a valid and effective approach for the treatment of pain and necessitates further study.

In summary, we have observed that 9 -THC enhances the antinociceptive effects of morphine and codeine in a synergistic fashion. This is the first report of a true synergistic interaction between oral 9 -THC and morphine or codeine, since previous studies have only examined one-dose combinations.

Much more work needs to be done to elucidate the mechanisms by which cannabinoids and opioids interact to produce analgesia. However, the implication that a combination of drugs may be more effective than either drug alone, and at the same time possibly reduce the occurrence of side effects, should provoke further study on analgesic drug interactions.”

http://jpet.aspetjournals.org/content/jpet/304/3/1010.full.pdf

http://healthdocbox.com/Substance_Abuse/71109245-Antinociceptive-synergy-between-9-tetrahydrocannabinol-and-opioids-after-oral-administration.html

Opioids and cannabinoids interactions: involvement in pain management.

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“Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems.

Cannabinoids and opioids are distinct drug classes that have been historically used separately or in combination to treat different pain states.

Indeed, it is widely known that activation of either opioid or cannabinoid systems produce antinociceptive properties in different pain models.

Moreover, several biochemical, molecular and pharmacological studies support the existence of reciprocal interactions between both systems, suggesting a common underlying mechanism.

Further studies have demonstrated that the endogenous opioid system could be involved in cannabinoid antinociception and recent data have also provided evidence for a role of the endogenous cannabinoid system in opioid antinociception.

These interactions may lead to additive or even synergistic antinociceptive effects, emphasizing their clinical relevance in humans in order to enhance analgesic effects with lower doses and consequently fewer undesirable side effects.

Thus, the present review is focused on bidirectional interactions between opioids and cannabinoids and their potent repercussions on pain modulation.”

https://www.ncbi.nlm.nih.gov/pubmed/20017728

http://www.eurekaselect.com/71318/article