Cannabis

[Paregoric Kid]

this post is my attempt to gather all relevant information on cannabis' effects with opiates/opioids.

Several studies have found that cannabinoids have analgesic effects in animal models, sometimes equivalent to codeine.25-29 Cannabinoids also seem to synergize with opioids, which often lose their effectiveness as patients build up tolerance. One study found morphine was 15 times more active in rats with the addition of a small dose of THC. Codeine was enhanced on the order of 900 fold.30

In 1990, researchers conducted a double-blind study comparing the antispasmodic and analgesic effects of THC, oral Codeine, and a placebo on a single patient suffering from a spinal cord injury.31 Their findings confirmed the analgesic effects of THC being "equivalent to codeine." A 1997 study made similar findings related to morphine.32

A 1999 article reviewing the body of scientific animal research concerning the analgesic effects of marijuana concludes that "[t]here is now unequivocal evidence that cannabinoids are antinociceptive [capable of blocking the appreciation or transmission of pain] in animal models of acute pain."33

In addition to it's analgesic properties, the IOM Report indicates that cannabis, like its synthetic cousin Marinol, can help treat the nausea often induced by opiate therapy, especially when other antiemetics prove ineffective.

25. Karst M et al (2003). Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain A Randomized Controlled Trial. JAMA. 290:1757-1762. 26. Richardson J et al (1998). Cannabinoids Reduce Hyperalgesia and Inflammation via Interaction with Peripheral CB1 Receptors. Pain. 75(1): 111-119.
27. Meng I et al (1998). An analgesic circuit activated by cannabinoids. Nature 395 381-383. http: //www.nature.com/cgitaf/DynaPage.taf?file= /nature/journal/v395/n670.../395381a0_r.htm
28. Klarreich E (2001). Cannabis spray blunts pain: Early trials suggest cannabis spritz may give relief to chronic pain sufferers. British Association for the Advancement of Science. 4 Sept.
29. Callahan R (1998). "How Does Marijuana Kill Pain?" Associated Press, October 4. http: //www.mapinc.org/drugnews/v98/n868/a07.html

30. Welch SP, Eads M (1999). Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Res. Nov. 27;848 (1-2): 183-90.
31. Maurer et al. (1990). Delta-9-tetrahydrocannabinol Shows Antispastic and Analgesic Effects in a Single Case Double-Blind Trial. European Archives of Psychiatry and Clinical Neuroscience 240:1-4
32. Holdcroft, A., op cit.
33. Martin WJ (1999). Basic Mechanisms of Cannabinoid-Induced Analgesia. International Association for the Study of Pain Newsletter, Summer. p. 89.
34. Cookson C (2001). High Hopes for Cannabis to Relieve Pain. British Association Science Festival in Glasgow, Financial Times, September 4, at National News pg. 4.


there are a few studies that show marijuana to be helpful at alleviating withdrawal symptoms. "Lichtmann et al. (2001) have shown that there seems to be a reciprocal relationship between the cannabinoid and opioid system relative to dependency. THC was able to block some of the withdrawal symptoms in morphine dependent mice,"
here are some studies: Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 2001p;298(3):1007-14.
Attenuation of precipitated abstinence in methadone-dependent rats by delta 9-THC.
Endogenous cannabinoid, 2-arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice.
Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

there are other studies that show THC and other chemicals in cannabis to bind at the mu opioid receptor.
here are some studies: Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors.
Cannabinoid agonists but not inhibitors of endogenous cannabinoid transport or metabolism enhance the reinforcing efficacy of heroin in rats.
Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats.
Repeated administration with Delta9-tetrahydrocannabinol regulates mu-opioid receptor density in the rat brain.
Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.
Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors.
Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification.from gw pharm makers of sativex:
In contrast to contemporary concerns that cannabis itself may have addictive potential, Indian hemp was used in the 19th century to treat dependencies on other substances. O'Shaughnessy observed benefit of cannabis extracts for delirium tremens in alcoholics (1), Clendinning shortly thereafter in morphine withdrawal (2), and Mattison in cocaine and chloral hydrate addiction (3). In fact, in an early 20th century text on addiction, the only mentions of cannabis were in relation to its therapeutic benefits (4). The LaGuardia Commission Report (5) contained an account of a group of 56 morphine and heroin addicts. Those who were cannabis-treated had less severe withdrawal symptoms and left the hospital earlier and in better shape than those receiving standard therapy.
Modern anecdotal support for utilisation of cannabis for addiction withdrawal continues to accrue (6-8). A formal study in Brazil (9) demonstrated that 17/25 subjects (68%) were successful in abrogating �crack' cocaine habits over the course of nine months through the use of cannabis, and claimed it able to allay cravings and induce other subjective benefits. Dreher in Jamaica has documented cannabis as the most effective treatment in stopping crack cocaine use in 33 women (10).
Cannabinoid interactions with the dopamine system have been offered as a possible mechanism for some of the beneficial effects of cannabis in opiate withdrawal (11). A recent study provides objective evidence of the ability of THC to mitigate opiate-withdrawal symptoms, and block the formation of physical dependency (12). Clinical trials of cannabis based medicine extracts in the treatment of opiate addiction seem amply justified.
References
1. O'Shaughnessy WB. On the preparations of the Indian hemp, or gunjah (Cannabis indica) ; Their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Transactions of the Medical and Physical Society of Bengal 1838-1840:71-102, 421-461.
2. Clendinning J. Observation on the medicinal properties of Cannabis sativa of India. Medico-Chirurgical Transactions 1843;26:188-210.
3. Mattison JB. Cannabis indica as an anodyne and hypnotic. St. Louis Medical and Surgical Journal 1891;61:265-271.
4. Crothers TD. Morphinism and narcomanias from other drugs: Their etiology, treatment, and medicolegal relations. Philadelphia: Saunders; 1902.
5. New York (N.Y.). Mayor's committee on marihuana., Wallace GB, Cunningham EV. The marihuana problem in the city of New York; sociological, medical, psychological and pharmacological studies. Lancaster, Pa.,: The Jaques Cattell press; 1944.
6. Mikuriya TH. Cannabis as a substitute for alcohol: a harm-reduction approach,. Journal of Cannabis Therapeutics 2004;4(1):(in press).
7. Mikuriya TH. Cannabis substitution. An adjunctive therapeutic tool in the treatment of alcoholism. Med Times 1970;98(4):187-91.
8. Grinspoon L, Bakalar JB. Marihuana, the forbidden medicine. Rev. and exp. ed. New Haven: Yale University Press; 1997.
9. Labigalini E, Jr., Rodrigues LR, Da Silveira DX. Therapeutic use of cannabis by crack addicts in Brazil. J Psychoactive Drugs 1999;31(4):451-5.
10. Dreher M. Crack heads and roots daughters: The therapeutic use of cannabis in Jamaica. Journal of Cannabis Therapeutics 2002;2(3-4):121-133.
11. French ED, Dillon K, Wu X. Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 1997;8(3):649-52.
12. Cichewicz DL, McCarthy EA. Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther 2003;304(3):1010-5.

Synergistic interactions of endogenous opioids and cannabinoid systems.

* Welch SP,
* Eads M.

Department of Pharmacology and Toxicology, Box 980613, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. S.Welch@hsc.vcu.edu

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.

PMID: 10612710 [PubMed - indexed for MEDLINE]

Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification
by
Cichewicz DL, Martin ZL, Smith FL, Welch SP
Department of Pharmacology and Toxicology,
Medical College of Virginia/Virginia Commonwealth University,
Richmond, Virginia, USA.
Jpn J Pharmacol 1999 Apr; 79(4):427-31

ABSTRACT

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.

http://jpet.aspetjournals.org/cgi/co...full/303/2/557 (http://jpet.aspetjournals.org/cgi/content/full/303/2/557)
Vol. 303, Issue 2, 557-562, November 2002
Synergy between µ Opioid Ligands: Evidence for Functional Interactions among µ Opioid Receptor Subtypes
Elizabeth A. Bolan, Ronald J. Tallarida and Gavril W. Pasternak
Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center and the Program in Neuroscience, the Weill Graduate School of Medical Sciences of Cornell University, New York, New York (E.A.B., G.W.P.), and Department of Pharmacology, Temple University Medical School, Philadelphia, Pennsylvania (R.J.T.)

[TappyTibbons]

pots makes me scared. I dunno why, i used to love it as a younger one. strange that putting a pile of powder in my nose doesn't bug me but a little organic matter does. Maybe it was all the hours i spent surrounded by hundreds of pounds of the stuff working at a medical dispensary in sf. personally I have always felt that it over rides the opiate high, but alot of people love the combo. But all that aside, good findings pk, you always seem to support your findings very well with factual citation. My guess, your a chem major (or similar?)

[Chipper]

if you get scared from smoking pot then actually *smoking more* works for me. I know it sounds bizare but it really helps

[nick]

Bro,I bet your fingers are tired after all that.



I can't help with scientific data,but my own experience is that cannabis does help with organic pain.



Otherwise,it's a senseatiser.If you feel good-you'll feel better.If you feel bad-you'll feel worse.

More to the point,how are you kid?

[OpiGuRu729]

I really like the combination of pot and opiate's i also have marinol (synthetic thc pills) i like to take them in combination with my medications and it seems to really help my pain... i also noticed if i dont have anything and i just take a marinol or smoke pot my withdraw isn't that bad.... i personally like mixing thc with opiate's it seems to make me feel higher for a lot longer... but thats personal preference i guess...

[Hammilton]

In my experience, I always found that cannabis' analgesic effects were due to the ability it gave my mind to ignore the pain.

I mean, I was always able to feel the pain, and it didn't really make the pain less painful, but it did make the pain feel different, like it wasn't connected to me or it was being covered up by some other sensory phenomena.

If that makes sense at all....

i did always feel that it over-rode whatever opiophoria I would have had otherwise.

You know what though, I had some really crappy pot not too long ago that didn't really affect my thought processes, or give me strobe-light vision or that out-of-body sorta thing I get at high doses (you know where you smoke so much and all of a sudden your vision becomes like watching a movie?)

Anyway, this crappy pot felt more like a valium than pot (as I'm used to it). It just relaxed me. Actually, i heard that a lot of people have that experience with pot. If pot didn't have it's psychedelic thought-pattern changing effects at all (or perhaps if it was easy to choose between psychedelic pot and benzo-pot), I might enjoy it a lot more.

But actually, when it comes to pot, I can really only enjoy it if I have taken 10mg or so of amphetamine sulfate to prevent that burnt-out, I-just-wanna-go-to-bed-and-not-move-again sorta feeling that I'm gonna get otherwise.

I like the comment that pot is a sensitizer. Not only in the respect that it amplifies postive and negative feelings, I think it also increases our connections to our senses. Sorta like making us notice things we otherwise wouldn't notice, or to cause us to focus on them more. Like with the after-images our eyes see. When I smoke pot purple and green splotches that in some form are always there, are suddenly big splotches.

I can't think of any other examples right now, but I think you'll get my concept. Or maybe just Nick will.. I dunno.

[TappyTibbons]

dude hammilton, when i used to smoke pot on the regular, the only way i could give someone an accurate description, was that i was watching myself, on a movie screen. like i was watching my life go on from a third person view. no one else knew what i was talking about and just called me a filthy degenerate stoner. glad I'm not the only one ha.

[Sitar]

Well, I do know that once I took too much Methadone, and was on the border of possible puking. So I took a hit or two of pot thinking it would cure the nausea enough to push me back into a no-puke zone.

Nope. The pot increased the high of the Methadone and shoved me straight into vomit territory, where I bombarded the toilet with emetic forces.

And then I was nodding like crazy.

[Paregoric Kid]

Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats
by
GSolinas M, Goldberg SR.
Preclinical Pharmacology Section,
Behavioral Neuroscience Research Branch,
National Institute on Drug Abuse,
Division of Intramural Research,
National Institute of Health,
Room 318, 5500 Nathan Shock Drive,
Baltimore, MD, 21224, USA.
Psychopharmacology (Berl). 2004 Dec 24

ABSTRACT

RATIONALE: Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems. OBJECTIVE: To investigate opioid receptor subtypes involved in the discriminative effects of THC. METHODS: Rats trained to discriminate 3 mg/kg i.p. of THC from vehicle using a two-lever operant drug-discrimination procedure, were tested with compounds that bind preferentially or selectively to either mu-, delta- or kappa-opioid receptors. RESULTS: The preferential mu-opioid receptor agonist heroin (0.3-1.0 mg/kg, i.p.), the selective delta-opioid receptor agonist SNC-80 (1-10 mg/kg, i.p.) and the selective kappa-opioid receptor agonist U50488 (1-10 mg/kg, i.p.) did not produce generalization to the discriminative effects of THC when given alone. However, heroin, but not SNC-80 or U50488, significantly shifted the dose-response curve for THC discrimination to the left. Also, the preferential mu-opioid receptor antagonist naltrexone (0.1-1 mg/kg, i.p.), the selective delta-opioid receptor antagonist, naltrindole (1-10 mg/kg, i.p.) and the kappa-opioid receptor antagonist nor-binaltorphimine (n-BNI, 5 mg/kg, s.c.), did not significantly reduce the discriminative effects of the training dose of THC. However, naltrexone, but not naltrindole or n-BNI, significantly shifted the dose-response curve for THC discrimination to the right. Finally, naltrexone, but not naltrindole or n-BNI, blocked the leftward shift in the dose-response curve for THC discrimination produced by heroin. CONCLUSIONS: mu- but not delta- or kappa-opioid receptors are involved in the discriminative effects of THC. Given the role that mu-opioid receptors play in THC's rewarding effects, the present findings suggest that discriminative-stimulus effects and rewarding effects of THC involve similar neural mechanisms.

INTERACTIONS BETWEEN CANNABINOID AND OPIOID RECEPTOR
SYSTEMS IN THE MEDIATION OF ETHANOL EFFECTS
by
Manzanares J, Ortiz S, Oliva JM, Perez-Rial S, Palomo T.
Servicio de Psiquiatria y Centro de Investigacion,
Hospital Universitario 12 de Octubre,
Avda. Cordoba s/n, 28041 Madrid, Spain.
Alcohol Alcohol. 2004 Nov 18

ABSTRACT

Over the past few years, advances in the investigation of the neurochemical circuits involved in the development and treatment of alcohol dependence have identified peptides and receptors as potential key targets in the treatment of problems related to alcohol consumption. The endogenous opioid system is modified by alcohol intake in areas of the brain related to reward systems, and differential basal levels of opioid gene expression are found in rodents with a high preference for ethanol. This suggests a greater vulnerability to alcohol consumption in relation to differences in genetic background. Further evidence of the involvement of opioid peptides in alcohol dependence is the ability of the opioid antagonist naltrexone to reduce alcohol intake in animal models of dependence and in alcohol-dependent patients. Abundant evidence indicates that the activation of cannabinoid receptors stimulates the release of opioid peptides, therefore the cannabinoid receptor antagonists may presumably alter opioid peptide release, thus facilitating the reduction of ethanol consumption. However, little is known about the effects of ethanol on the endogenous cannabinoid system, the vulnerability of cannabinoid receptors to alcohol intake or their neurochemical implications in reducing consumption of alcohol. In this paper, we review the role of opioid and cannabinoid receptor systems, their vulnerability to alcohol intake and the development of dependence, and the targeting of these systems in the treatment of alcoholism.

Cannabidiol is an allosteric modulator at
mu- and delta-opioid receptors
by
Kathmann M, Flau K, Redmer A, Trankle C, Schlicker E.
Department of Pharmacology and Toxicology,
School of Medicine, University of Bonn,
Reuterstr. 2b, 53113, Bonn, Germany,
m.kathmann@uni-bonn.de.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Feb 18;

ABSTRACT

Ohe 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, (-)-Delta(9)-tetrahydrocannabinol (THC; another major constituent of cannabis) and rimonabant (a cannabinoid CB(1) receptor antagonist) were studied. In mu opioid receptor binding studies on rat cerebral cortex membrane homogenates, the agonist (3)H-DAMGO bound to a homogeneous class of binding sites with a K(D) of 0.68+/-0.02 nM and a B(max) of 203+/-7 fmol/mg protein. The dissociation of (3)H-DAMGO induced by naloxone 10 muM (half life time of 7+/-1 min) was accelerated by cannabidiol and THC (at 100 muM, each) by a factor of 12 and 2, respectively. The respective pEC(50) values for a half-maximum elevation of the dissociation rate constant k(off) were 4.38 and 4.67; (3)H-DAMGO dissociation was not affected by rimonabant 10 muM. In delta opioid receptor binding studies on rat cerebral cortex membrane homogenates, the antagonist (3)H-naltrindole bound to a homogeneous class of binding sites with a K(D) of 0.24+/-0.02 nM and a B(max) of 352+/-22 fmol/mg protein. The dissociation of (3)H-naltrindole induced by naltrindole 10 muM (half life time of 119+/-3 min) was accelerated by cannabidiol and THC (at 100 muM, each) by a factor of 2, each. The respective pEC(50) values were 4.10 and 5.00; (3)H-naltrindole dissociation was not affected by rimonabant 10 muM. 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.

Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use
by
Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL.
1Department of Clinical Neuroscience,
Psychiatry Section, Karolinska Institute,
Stockholm, Sweden.
Pharmacogenomics J. 2006 Feb 14;

ABSTRACT

Fetal development is a period sensitive to environmental influences such as maternal drug use. The most commonly used illicit drug by pregnant women is marijuana. The present study investigated the effects of in utero marijuana exposure on expression levels of opioid-related genes in the human fetal forebrain in light of the strong interaction between the cannabinoid and opioid systems. The study group consisted of 42 midgestation fetuses from saline-induced voluntary abortions. The opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval). Prenatal cannabis exposure was significantly associated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure primarily influenced the kappa receptor mRNA with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure could be discerned in the present study group. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially impair opioid-related genes in distinct brain circuits that may have long-term effects on cognitive and emotional behaviors.

Motivational Effects of Cannabinoids and Opioids on Food Reinforcement Depend on Simultaneous Activation of Cannabinoid and Opioid Systems
by
Solinas M, Goldberg SR.
1Preclinical Pharmacology Section,
Behavioral Neuroscience Branch,
National Institute on Drug Abuse, Intramural Research Program,
National Institutes of Health,
Department of Health and Human Services,
Baltimore, MD, USA.
Neuropsychopharmacology. 2005 Apr 6

ABSTRACT

Strong functional interactions exist between endogenous cannabinoid and opioid systems. Here, we investigated whether cannabinoid-opioid interactions modulate motivational effects of food reinforcement. In rats responding for food under a progressive-ratio schedule, the maximal effort (break point) expended to obtain 45 mg pellets depended on the level of food deprivation, with free-feeding reducing break points and food-deprivation increasing break points. Delta-9-tetrahydrocannabinol (THC; 0.3-5.6 mg/kg intrapeitoneally (i.p.)) and morphine (1-10 mg/kg i.p.) dose-dependently increased break points for food reinforcement, while the cannabinoid CB1 receptor antagonist rimonabant (SR-141716A; 0.3-3 mg/kg i.p.) and the preferential mu-opioid receptor antagonist naloxone (0.3-3 mg/kg i.p.) dose-dependently decreased break points. THC and morphine only increased break points when food was delivered during testing, suggesting that these treatments directly influenced reinforcing effects of food, rather than increasing behavior in a nonspecific manner. Effects of THC were blocked by rimonabant and effects of morphine were blocked by naloxone, demonstrating that THC's effects depended on cannabinoid CB1 receptor activation and morphine's effects depended on opioid-receptor activation. Furthermore, THC's effects were blocked by naloxone and morphine's effects were blocked by rimonabant, demonstrating that mu-opioid receptors were involved in the effects of THC and cannabinoid CB1 receptors were involved in the effects of morphine on food-reinforced behavior. Thus, activation of both endogenous cannabinoid and opioid systems appears to jointly facilitate motivational effects of food measured under progressive-ratio schedules of reinforcement and this facilitatory modulation appears to critically depend on interactions between these two systems. These findings support the proposed therapeutic utility of cannabinoid agonists and antagonists in eating disorders

[tasteuvheaven]

pots makes me scared. I dunno why, i used to love it as a younger one. strange that putting a pile of powder in my nose doesn't bug me but a little organic matter does. Maybe it was all the hours i spent surrounded by hundreds of pounds of the stuff working at a medical dispensary in sf. personally I have always felt that it over rides the opiate high, but alot of people love the combo. But all that aside, good findings pk, you always seem to support your findings very well with factual citation. My guess, your a chem major (or similar?)

when i smoke..it always makes me anxious..dunno why..when i was young..15ish i used to smoke alllll the time and it relaxed me and made me giddy and giggley...wish i still got the same effect...i have tried smokin after i took a few pills and i like the feeling, makes the pills seem to work longer and i feel reallly relaxed..just cant smoke without the pills...hubby agrees with you...he wont smoke if he is going to or already has taken pills...says it takes away from the pills...over rides the pills.

[chemboy7]

Bro,I bet your fingers are tired after all that.

I bet his copy/paste function is tired. Hahaha

[OxyContinuously]

I like that abstract/article, and personally, I like pot by itself, in combo with opes is good too.

But to this day, i love a blunt in the afternoon, whether or not there is anything "under" it. I dunno, guess ijust love weed.


later

[djnarkotik]

cannabis is alright, good sensory enhancer. But there is so much cannabis everywhere. especially here in canada, i dont even do it much and i have a stash. I would trade some weed for opiates anyday though. jus wish half as many people that did cannabis do opiates.

[exit-chronicpain]

This is why I would be stone dead by now if it weren't for the miracle of Cannabis. My pain is controlled at least as my by the G13, SAGE, Caramella, Stardust 13 and other medicinal strains as it is by the Oxycontin, Kadian, MS Contin, Dilaudid, Roxicodone, Lortab, Fentanyl Patches, or even the Holy Grail Opana, which I am so desperately trying to get switched to permanently but have to wait for my insurance provider to start covering it....if they ever do.

The next week or so may tell me for sure. I am praying desperately that I will be able to use the medication switch to get my next month's meds early, before I go on a week-long vacation right in the middle of which would be my normal refill time for 3 of my four pain medications. I will be almost 1,200 miles away. Getting these medications there is difficult and I have a special relationship with my local pharmacy & pharmacists.

Pray for me, my friends. Pray that Opana will be covered as a Preferred Drug, with no limits, in both ER and IR versions, as of June 1st by my provider. Because otherwise I am in deep shit. And using cannabis even with a vaporizer and a car adapter, is extremely tricky on the road.

[exit-chronicpain]

I discovered cannabis' amazing ability to moderate pain when I had a horrible bike accident on the road in a city I used to live in....I lost almost all the skin on one of my calves, right down to the muscle and bone. A Class A-1 "Call 911" type road rash.

I managed to ride 3.7 miles back home on my road bike, pouring blood so fast that even at 25MPH I was leaving a visible blood trail. I arrived back at my apartment doorstep where my wife answered the door and her jaw dropped to the floor when she saw my leg.

As we carefully cleaned and bandaged my leg, she set up a bong for me. I used it liberally throughout the cleaning process and the effect it had on simply excruciating, intolerable agony was like nothing I had ever experienced before. I had been on Vicodin for my wisdom tooth extraction, and later I would be on it twice for my two severe Staph infections (first my knee and then two years later my groin/pelvis lymph, nerve & artery structures called the Spermatic Cord which leads directly to the heart).....together they work very well, but if I had to choose only one or the other it would be hard to say that Opiates are the obvious choice. Cannabis is irreplaceable in the chronic pain sufferer's arsenal.

[limestoneman]

Otherwise,it's a senseatiser.If you feel good-you'll feel better.If you feel bad-you'll feel worse.


I couldn't agree more.

[Paregoric Kid]

Involvement of cannabinoid (CB1)-receptors in the development and maintenance of opioid tolerance.

Trang T (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Trang%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Sutak M (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Sutak%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Jhamandas K (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Jhamandas%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Sustained exposure to opioid agonists such as morphine increases levels of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn, a response implicated in the development of opioid tolerance and physical dependence. Recent evidence suggests that both the opioid-induced increase in CGRP and the development of opioid physical dependence are suppressed by blockade of spinal cannabinoid (CB1)-receptors. The present study examined whether CB1-receptor activity also has a role in the development of opioid tolerance. In rats implanted with spinal catheters, repeated acute injections of morphine (15 microg) delivered over 4 h resulted in a rapid decline of thermal and mechanical antinociception and a significant loss of analgesic potency, reflecting development of acute opioid tolerance. In another set of experiments, chronic administration of spinal morphine (15 microg) once daily for 5 days produced a similar loss of analgesic effect and a marked increase in CGRP-immunoreactivity in the superficial laminae of the dorsal horn. Consistent with the in vivo findings, primary cultures of adult dorsal root ganglion (DRG) neurons exposed to morphine for 5 days showed a significant increase in the number of CGRP-immunoreactive neurons. Co-administration of acute or chronic morphine with a CB1-receptor antagonist/inverse agonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM-251), inhibited the development of both acute and chronic analgesic tolerance. In animals already exhibiting tolerance to morphine, intervention with AM-251 restored morphine analgesic potency. Co-administration with AM-251 attenuated the morphine-induced increase in CGRP-immunoreactivity in the spinal cord and in DRG cultured neurons. Collectively, the results of this study suggest that activity of endocannabinoids, mediated via CB1-receptors, contributes to both the development and maintenance of opioid tolerance by influencing the opioid-induced increase in spinal CGRP.

[Paregoric Kid]

here is a really interesting video on how cannabis interacts with opioids:
Opiate & Cannabinoid Interactions, with Sandra Welch PhD @ the 2004 Cannabis Therapeutics Conference http://www.youtube.com/watch?v=JRFnGS1XPe4

[pain-pateint]

PK --

I was at that conference in 2004 in Charlotteville, VA, when Sandra presented those findings. Another presenter at that conference (Patients Out of Time put it on) talked about drug companies trying to come up with a combination product of an opiate and a cannabinoid, just as opiates are often combined with acetaminophen. I think we will see a lot of new drugs that manipulate the CB system.

M

[Paregoric Kid]

The Surprising Effect Of Marijuana On Morphine Dependence

Posted on: Monday, 6 July 2009, 11:33 CDT
Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth. This has been shown by a study carried out by Valérie Daugé and her team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / INSERM) in the journal Neuropsychopharmacology. The findings could lead to therapeutic alternatives to existing substitution treatments.

In order to study psychiatric disorders, neurobiologists use animal models, especially maternal deprivation models. Depriving rats of their mothers for several hours a day after their birth leads to a lack of care and to early stress. The lack of care, which takes place during a period of intense neuronal development, is liable to cause lasting brain dysfunction. Valérie Daugé's team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (UPMC / CNRS / Inserm) analyzed the effects of maternal deprivation combined with injections of tetrahydrocannabinol, or THC, the main active principle in cannabis, on behavior with regard to opiates.

Previously, Daugé and her colleagues had shown that rats deprived of their mothers at birth become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent
. In addition, there is a correlation between such behavioral disturbances linked to dependence, and hypoactivity of the enkephalinergic system, the endogenous opioid system.

To these rats, placed under stress from birth, the researchers intermittently administered increasingly high doses of THC (5 or 10 mg/kg) during the period corresponding to their adolescence (between 35 and 48 days after birth). By measuring their consumption of morphine in adulthood, they observed that, unlike results previously obtained, the rats no longer developed typical morphine-dependent behavior. Moreover, biochemical and molecular biological data corroborate these findings. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC.

Such animal models are validated for understanding the neurobiological and behavioral effects of postnatal conditions in humans. In this context, the findings point to the development of new treatments that could relieve withdrawal effects and suppress drug dependence.

The enkephalinergic system produces endogenous enkephalins, which are neurotransmitters that bind to the same receptors as opiates and inhibit pain messages to the brain.

[PiLL CLiNToN]

Good find intresting this is why the marijuana plantt is the greatest plant ever! we find more and more uses of it than any other herb!:D:Dp.s boston was rated 2nd in best quality marijuana p.s im realllllly baked

[got_bags?]

here is a really interesting video on how cannabis interacts with opioids:
Opiate & Cannabinoid Interactions, with Sandra Welch PhD @ the 2004 Cannabis Therapeutics Conference http://www.youtube.com/watch?v=JRFnGS1XPe4

Great video. I definitely find that smoking greatly increases my opio buzz. However, I'm am everyday smoker and rarely don't combine the two, so i have little baseline for comparison.

[duck]

Otherwise,it's a senseatiser.If you feel good-you'll feel better.If you feel bad-you'll feel worse.



I agree completely...never thought of it that way, thanks Nick.

[Bud]

I could never ever imagine how expensive my half ounce every 2 days would be in the US, here its 100 for a half ounce of kush if im in between harvests.

shitty thing is I would love new york for 9000 a pound instead of 3 down here :P ( Canada eh)

[Papa Verine]

shitty thing is I would love new york for 9000 a pound instead of 3 down here :P ( Canada eh)

Bud... Do you mean to tell us you are below New York and in Canada?

[Paregoric Kid]

well I agree that in some people it does act as a "sensitizer" that if you feel good already then you'll feel even better or if you feel bad already then you'll feel even worse. I think its just that some people react that way to it, perhaps they are smoking a strain that gives them anxiety or maybe that is just how they react to cannabis. the actions of drugs and neurotransmitters can vary from person to person because everyone has genetic differences that produce differently shaped receptors (for example, not everyones mu or cannabinoid receptors are exactly alike so drugs and neurotransmitters bind and interact with them differently) and that probably accounts for why people react differently to things. a lot of people, including myself, feel much better after smoking even if I was feeling like shit. and that applies to feeling bad from depression or being in pain or wd, smoking some cannabis always makes me feel much better.
I recently read an article about the new synthetic cannabinoids in one of the bigger cannabis magazines and it seemed kind of unfair towards them. they tried to say that they could be unsafe and that they are only good for getting you high and have no medical value. sounds just like the bullshit the government and anti-drug people say about cannabis. they act on the same receptors as THC and cause similar effects, so it should follow that they have similar therapeutic benefits. how are they any different from the synthetic cannabinoid nabilone (Cesamet) or synthetically produced THC (dronabinol). I have found that with the JWH and CP chemicals I've tried so far they seem to definitely have analgesic effects and are also good for nausea, depression, and anxiety (unless you take too much or normally get anxiety from cannabis) and likely other symptoms that are treated with cannabis, dronabinol, and nabilone. some of the JWH and CP chemicals have been researched a little, preliminary evidence seems to show that some of the more popular ones are not carcinogenic or any more dangerous than THC. so it would appear they are fairly non-toxic. either way there should still be more research done on them and I would hope they can continue to be sold legally without a prescription and eventually become approved as an uncontrolled OTC medicines.

[DCBA]

PK - Good articles and great reading.

Too bad cannabis gives an anxious high since i stopped smoking for 3 weeks 6 months ago, till that date i was smoking 3 to 4 grams of 15-20% buds everyday and felt good on them. I also loved the synergy between opioids and cannabis.
Too bad i cant count as cannabis as a daily high nowadays, it just leaves too anxious and a little paranoid, and so i rarely smoke it. I consider loosing cannabis as a daily drug one of my great losts of all times... Since 25 years ago that i was a daily smoker.
What its strange is that this has happened when i stopped smoking for 3 weeks and till that date everything was alright with the high, but after the date cannabis is just too powerful. :(

[Bud]

Bud... Do you mean to tell us you are below New York and in Canada?

swim is a Canadian yes, and he loves growing :)

[duck]

PK - Good articles and great reading.

Too bad cannabis gives an anxious high since i stopped smoking for 3 weeks 6 months ago, till that date i was smoking 3 to 4 grams of 15-20% buds everyday and felt good on them. I also loved the synergy between opioids and cannabis.
Too bad i cant count as cannabis as a daily high nowadays, it just leaves too anxious and a little paranoid, and so i rarely smoke it. I consider loosing cannabis as a daily drug one of my great losts of all times... Since 25 years ago that i was a daily smoker.
What its strange is that this has happened when i stopped smoking for 3 weeks and till that date everything was alright with the high, but after the date cannabis is just too powerful. :(

This has happened to EVERY singly marijuana smoker I know, and that's pretty much all of my acquaintences.

They smoked like champions for years, and then, one day, usually after some catalyst (in your experience, the 3 week break, they become incredibly anxious and paranoid after smoking.

This too happened to me, serverely I may note. However, like the dedicated drug addict I am, I continued smoking through it. Now, the physical symptoms are completely gone, and the psychological ones are much more under control. Like, I used to get a ridiculously fast heart rate that would drive me crazy, that is completely gone now. However, I do get paranoid, but have the foresight to see the irrationality in the paranoia and can decently control it.

The synergy between opiates and weed is the only thing that allows my addiction to be somewhat satisfying. Without weed, my tolerance just laughs in my face after I empty my bank account and don't feel a damn thing.

/ramble