Anyone know anything about Opiode resistance?

[Faultydesign]

I have chronic lumbar back pain due to a bulged disk. Because of this I am prescribed Hydrcodone for pain. However, The pills do nothing for me unless taken in far too much excess. I do not enjoy having to take 8x my required dose to get alleviation. However, I do not that it is the severity of my pain that is causing this problem. For example, when I smoke Cannabis the pain subsides for a good deal of time. Is it possible that my body has a natural resistance to opium based products? Note I have also tried oxycotin and felt little to effect from a 20mg pill.
Any information about alternative pain solutions I would be highly in favor of.
I am reluctant to use marijuana even solely medicenely because the career I am going into very much frowns upon usage of the substance.

[birdgirl73]

I have the same resisitance, and for a long time I just thought it was me, and then finally an anesthesiologist and a pharmacology professor told me that were a good many people who were naturally resistant to opioids just like there are others who are naturally susceptible and who, as a result, are more susceptible to addiciton to them. Drugs containing opioids or derivatives don't do a thing for me when administered for pain (I wouldn't take them recreationally). Consequently, my favorite pain medicine is ibuprofen.

I believe I read somewhere on here that cannabis is supposed to contribute to making opioid receptors more sensitive, which is why some folks believe it to be a gateway drug to addiction to harder substances like heroin. I don't know if that's true or not, but I do know there are folks who are resistant to opioids because I'm one of them, too.

[beachguy in thongs]

There is currently substantial evidence that Cannabis sativa derivates act on brain reward in a way very similar to other drugs of abuse and exert numerous pharmacological effects through their interaction with various neurotransmitters and neuromodulators. Among them, the endogenous opioids seem to play an important role in modulating the addictive properties of cannabinoids. Given the plethora of research activity on such a topic, this brief review is necessarily focused on cannabinoid/opioid interaction in reward-related events and restricted to the recent literature. Recent findings from our and other laboratories concerning cannabinoid reinforcing effects as revealed by behavioral animal models of addiction are here summarized. Evidence is then provided demonstrating a functional cross-talk between the cannabinoid and opioid systems in the mutual modulation of the addictive behavior; accordingly, very recent data from transgenic mice lacking either the cannabinoid CB1 or opioid receptors are also presented. Finally, the role of the endogenous cannabinoid system in relapse to opioids is investigated by means of extinction/reinstatement animal models following a period, even prolonged, of drug abstinence. Altogether, the reviewed studies provided a better understanding of the neurobiological mechanisms involved in cannabinoid actions and revealed a bidirectional interaction between the endogenous cannabinoid and opioid systems in reward that extends to central mechanisms underlying relapsing phenomena. Challenges for the future involve elucidation of the neuroanatomical substrates of cannabinoids action, even in light of the therapeutic potential of these compounds.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15581410&query_hl=4&itool=pubmed_docsum

The mechanism of action of cannabidiol, one of the major constituents of cannabis, is not well understood but a noncompetitive interaction with mu opioid receptors has been suggested on the basis of saturation binding experiments. The aim of the present study was to examine whether cannabidiol is an allosteric modulator at this receptor, using kinetic binding studies, which are particularly sensitive for the measurement of allosteric interactions at G protein-coupled receptors. In addition, we studied whether such a mechanism also extends to the delta opioid receptor. For comparison, (-)-Delta9-tetrahydrocannabinol (THC; another major constituent of cannabis) and rimonabant (a cannabinoid CB1 receptor antagonist) were studied. In mu opioid receptor binding studies on rat cerebral cortex membrane homogenates, the agonist 3H-DAMGO bound to a homogeneous class of binding sites with a KD of 0.68+/-0.02 nM and a Bmax of 203+/-7 fmol/mg protein. The dissociation of 3H-DAMGO induced by naloxone 10 microM (half life time of 7+/-1 min) was accelerated by cannabidiol and THC (at 100 microM, each) by a factor of 12 and 2, respectively. The respective pEC50 values for a half-maximum elevation of the dissociation rate constant k(off) were 4.38 and 4.67; 3H-DAMGO dissociation was not affected by rimonabant 10 microM. In delta opioid receptor binding studies on rat cerebral cortex membrane homogenates, the antagonist 3H-naltrindole bound to a homogeneous class of binding sites with a KD of 0.24+/-0.02 nM and a Bmax of 352+/-22 fmol/mg protein. The dissociation of 3H-naltrindole induced by naltrindole 10 microM (half life time of 119+/-3 min) was accelerated by cannabidiol and THC (at 100 microM, each) by a factor of 2, each. The respective pEC50 values were 4.10 and 5.00; 3H-naltrindole dissociation was not affected by rimonabant 10 microM. The present study shows that cannabidiol is an allosteric modulator at mu and delta opioid receptors. This property is shared by THC but not by rimonabant.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16489449&query_hl=4&itool=pubmed_docsum

[Faultydesign]

Thank you for your imput you two, birdgirl how would I go about bringing up a possible opoide resistance to my healthcare provider?

[beachguy in thongs]

Sorry, I put the wrong second study.

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats.

* Ellgren M,
* Spano SM,
* Hurd YL.

Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Stockholm, Sweden.

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mug/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mug/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mug/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

Neuropsychopharmacology advance online publication, 05 July 2006; doi:10.1038/sj.npp.1301127.

Neuropsychopharmacology. 2006 Jul 5; [Epub ahead of print]
PMID: 16823391 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16823391&query_hl=7&itool=pubmed_docsum

[Nullific]

Interesting research indeed but its a damn shame that the media is using these findings to perpetuate this "marijuana is a gateway drug" bullshit. Once the mind has been introduced to any psychoactive substance chances are that it will be more prepared for any other psychoactive substance. Besides, if I was a lab rat given a life-time supply of pharmaceutical grade diamorphine I would go fucking wild.

Opioid tolerance is dependent on past or present usage and most importantly individual biochemistry. These are the safest, most effective pain relievers known to man but unfortunately law and society prevent many people from getting the opioids and relieve they are entitled to. Due to media hype and ignorance many doctors are reluctant to prescribe opioids even to those who really need them.

Faultydesign,
I am assuming your prescription is for 5/500 hydrocodone/APAP. This is the lowest dose available and simply isn't suitable for treatment of moderate to severe pain. If you get relief from 30mg of hydrocodone then ~20mg of instant-release oxycodone should provide relief at a similar level. So long as you don't look like a fiend you should be able to tell your healthcare provider that your current prescription just is not working very well. You might also mention that you tried a higher dosage successfully but are concerned about the amount of acetaminophen you would be ingesting if you did this frequently. He may be persuaded to prescribe a higher dosage of hydrocodone (they come up to 10mg) or something else entirely. Good luck.

[beachguy in thongs]

I, kind of, see it as Pot being a gateway to a shitty coke experience, as being compared to no-Pot being a gateway to an excellent coke experience.