drfeelgood1
Bluelighter
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- Oct 15, 2005
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Loperamide IS NOT an opiate...
A guide to opioid addiction treatments and other medications used for withdrawal
- Thread starter cashtothemoney
- Start date
PIC
Bluelighter
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- Feb 7, 2005
- Messages
- 669
I'm sorry but I really don't think that you have to taper with Immodium, do you have any scientific literature to back that up? On the other side, I remember reading somewhere that it is an opiate which has a quite similar chemical structure to fentanyl.
TheTripDoctor
Bluelighter
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- Jan 3, 2001
- Messages
- 792
OK look fuckers, loperamide is a piperidine, its not related to phenathrenes like moprhine or oxycodone, but then again neither is fentanyl, so whats your definition of opiate?
You can discount what i say all you want, but i have plenty of credibility here both on this board and from real life experience and education, and i know for absolute certain that loperamide IS ACTIVE, it WILL stop withdrawl, not just symptoms, withdrawal itself. I've theorized as to the route of its action numerous times, one of the following is true.
A) it does make it into the brain in amounts far less than huge doses with enzymatic inhibition
B) a metabolite of it makes it into the brain in normal doses with enzymatic inhibition, if you stop metabolism of the primary route, secondary routes then become active in larger percentage.
C) loperamide or a metabolite bind to opiate receptors peripherally, and cause CNS activity that way.
Every single one of those routes is both possible and likely, so dont post crap about drugs having to get into the CNS for activity, and yes loperamide likely DOES get into the brain in only slightly higher than normal doses if you use an enzyme inhibitor like cimetidine, i have 3 years experience screwing with it every way possible.
And yes, if i had stopped taking it by itself there would have been withdrawl from it alone, so by implied logic you therefor have to taper it if youve taken enough for a period of time.
6mg isnt going to do shit though, in a tollerant person 6mg isnt even going to be capable of putting a dent in withdrawal, your not going to get to the point of needing to taper if you only take 6mg.
48mg, yes, that point you would need to taper it back down, because 48mg is active.
You can discount what i say all you want, but i have plenty of credibility here both on this board and from real life experience and education, and i know for absolute certain that loperamide IS ACTIVE, it WILL stop withdrawl, not just symptoms, withdrawal itself. I've theorized as to the route of its action numerous times, one of the following is true.
A) it does make it into the brain in amounts far less than huge doses with enzymatic inhibition
B) a metabolite of it makes it into the brain in normal doses with enzymatic inhibition, if you stop metabolism of the primary route, secondary routes then become active in larger percentage.
C) loperamide or a metabolite bind to opiate receptors peripherally, and cause CNS activity that way.
Every single one of those routes is both possible and likely, so dont post crap about drugs having to get into the CNS for activity, and yes loperamide likely DOES get into the brain in only slightly higher than normal doses if you use an enzyme inhibitor like cimetidine, i have 3 years experience screwing with it every way possible.
And yes, if i had stopped taking it by itself there would have been withdrawl from it alone, so by implied logic you therefor have to taper it if youve taken enough for a period of time.
6mg isnt going to do shit though, in a tollerant person 6mg isnt even going to be capable of putting a dent in withdrawal, your not going to get to the point of needing to taper if you only take 6mg.
48mg, yes, that point you would need to taper it back down, because 48mg is active.
Last edited:
PIC
Bluelighter
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- Feb 7, 2005
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- 669
"i have plenty of credibility here both on this board and from real life experience and education"
Yeah, whatever man, do you have scientific literature to back it up? I just want to see where it says that one can withdrawal from Immodium. Forget your credibility, that is quite subjective.
Yeah, whatever man, do you have scientific literature to back it up? I just want to see where it says that one can withdrawal from Immodium. Forget your credibility, that is quite subjective.
EudoXia
Bluelighter
- Joined
- Dec 18, 2003
- Messages
- 778
TripDoctor,
What dose of loperamide would you recomend someone start out if they were taking around 60mg of hydrocodone/daily, but quit taking it and is in w/ds? I've used loperamide to help stop up my liquid G.I. tract, but have never noticed it helping with anything else. Just keeps you from shitting the bed when you are in withdrawal, basically.
What dose of loperamide would you recomend someone start out if they were taking around 60mg of hydrocodone/daily, but quit taking it and is in w/ds? I've used loperamide to help stop up my liquid G.I. tract, but have never noticed it helping with anything else. Just keeps you from shitting the bed when you are in withdrawal, basically.
cashtothemoney
Bluelighter
- Joined
- Jan 16, 2006
- Messages
- 172
-bump-
this might be able to help someone...
this might be able to help someone...
AlphaOdure
Bluelighter
- Joined
- Jul 7, 2003
- Messages
- 1,412
TABLE OF CONTENTS
Description and Pharmacology of Opioidergic Drug Replacement Therapies
Methadone
Levoacetylmethadol (LAAM)
Buprenorphine
Propoxyphene
Codeine
Tramadol
Full Agonist Opioids
Description and Pharmacology of Non-Opioidergic Therapies
Ibogaine/18-methoxycoronaridine
Naltrexone Maintenance
Rapid Detoxification
Listing of Pharmaceutical and Herbal Treatments for Withdrawal
Opioid Based Medicines (For treatment of dysphoria)
Non-Opioid Based Medicines (Classified by the symptomatic relief they provide; Generally non-dependence prone)
-Insomnia/Anxiety/Hypertension
-Diarrha/Abdominal Cramping
-Rhinorrhea (Increased salivation)/Lacrimation (Increased tear production)
-Pyretic Sensations (Chills, fever)
-Nausea
-Aches, Pains
Non-Barbituate & Non-Benzodiazepine M03B Class Muscle Relaxants (May help with anxiety, insomnia, and pain; Some may be habit forming)
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OPIOIDERGIC DRUG REPLACEMENT THERAPIES
Methadone
--------------------------------------
Methadone is a diphenylheptane-derivative, a potent mu-agonist opioid, and both an effective treatment for narcotic addiction and pain. Its duration of action is quite long, lasting anywhere from 12 - 36 hours, based on dosage. It has similar risks to that of traditional opioid narcotics regarding dependency, tolerance, and withdrawal. However, b/c longer acting drugs take longer to metabolize; less drug is introduced during a given interval of time--the result is a longer retained but less intense psychoactive effect. An example of this: dia-morphine (heroin) is metabolized more quickly than morphine due to its attatched diactyl-group; the result is heroin's shorter duration in action but more intense effects, producing more euphoria and a stronger rush.
Methdone also has a unique pharmacological action in having minor, non-competitive antagonist activity at NMDA receptors, similar to but weaker than drugs like dextromethorphan and ketamine. In a small percentage of people this can facilitate a varied response of unwanted side effects including: amnesia, catalepsy (sensation of rigid muscles), confusion, dysphoria, agitation, ataxia, and/or catatonia.
However, methadone is also is a weak inhibitor of serotonin and norepinephrine reuptake. These properties give methadone an added benefit of being a minor anti-depressant. But because hypertension associated with withdrawal is attributed to elevated norepinephrine levels, methadone's SNRI activity can cause persisting, residual stimulation and hypertensive symptoms for a few days if MRT is started after a bout of withdrawal.
Methadone does have an added benefit of a blocking other opioids at and around 70 mg. Methadone isn't a competitive agonist, so it will not completely block other mu-agonists or precipitate withdrawal. This exact mechanism of blocking isn't known, but is sometimes attributed, and controversly so, to the fact that there is usually a ceiling effect on the euphoria and analgesia caused by most opioids that attain their primary psychoactive action from the activity of their corresponding metabolites. And b/c only so much of a certain molecule can be converted into a metabolite at once, a ceiling effect comes into play. But drugs which are active in themselves are still blocked to some degree by methadone. Other theories involving a maximum limit on immediate mu agonism are proposed but have no significant scientific evidence to date.
Unfortunately, withdrawal from methadone is notoriously unpleasant. If not tapered correctly, withdrawal and extreme discomfort can last up to 1 - 4 weeks. But even when done properly it can cause malaise-conditions (dysphoria associated with drug use) for 3 - 10 days. This disadvantage in MMT withdrawal can potentially instigate a relapse.
Also, there has been one reported case of death from methadone withdrawal (>175 mg daily intake). The victim died from complications during episodes of seizuring. But due to her unfortunate circumstances it was not known whether she was previously epileptic (she was incarcerated and had no known family or doctors to contact for medical information); thus it can not be definitively concluded if her death was directly due to methadone withdrawal or epilepsy complications.
So generally speaking, methadone is more effective as a long term DRT maintenance medication due to its full mu-opioid agonist pharmacology. It can cause euphoria and has relatively high abuse potential, but when used properly these effects can be minimized. But methadone can still contribute to complications when tapering b/c of its similarity in action to typical narcotic analgesics. Therefore, methadone maintenance is more suited towards substituting, regulating, and minimizing illicit opioid addiction rather than promoting eventual abstinence. Experimental, case-study evidence for this can be found at http://opioids.com/methadone/tapering.html.
Levoacetylmethadol (LAAM)
--------------------------------------
LAAM is also a diphenylheptane-derivative, like methadone and propoxyphene. Its risks and benefits are nearly identical to that of methadone's but with one major difference. LAAM's duration of action is roughly double that of its counterpart and only requires dosing 3 - 4 times a week. Generally though, it is less favored to methadone (i tend to agree) b/c of its tendency to take longer to relieve withdrawal.
Recently, LAAM's metabolites have shown signs of cardiotoxicity at normal maintenance doses, therefore it has since been discontinued for medical use in the U.S. but is still available in MMT clinics. There are also suspicions of hepatoxicity being caused by LAAMMT as well. Its dextro isomer has shown less toxicity but has significantly less duration of action and more abuse-potential; methadone is more appropriate if LAAM isn't well tolerated.
Buprenorphine
--------------------------------------
Buprenorphine belongs to a small group of opioids known as benzomorphane derivatives. Buprenorphine is a novel medication b/c it has both mu-opioid agonist and antagonist properties. It is highly competitve at receptor sites, making it similar to nalaxone and naltrexone. But unlike these drugs, it also has an inherit mu-opioid agonist effect. It produces typical narcotic analgesia at lower doses and can ward off withdrawal for up to 48 hours.
Buprenorphine's competitive affinity for opioid receptors means that it has an advantage in the fact that full-opioid agonists will have no neurological action when taken during maintenance therapy. However, at amounts less than 2 mg this effect is less pronounced and wears off 12 - 24 hours after last dose.
Because buprenorphine is not a full mu-opioid agonist, it has a ceiling limit on its effects. Over 8 - 16 mg, the analgesic and euphoric properties do not increase; only duration in action is extended. Also, buprenorphine's unique pharmacological profile means that once BMT is mantained for a few weeks euphoria, sedation, and the potential for abuse becomes of relatively less significance.
Buprenorphine also has action at the ORL1 nociceptin (a newly discovered opioid receptor-class) receptors as a partial agonist and antagonist. In low doses, this can result in novel anti-depressant like effect; but when sudden, higher doses are used during maintenance therapy, this can result in lethargy, sedation, and mild dysphoria. This has an added detering effect in patients seeking to abuse buprenorphine when in maintenance therapy.
Buprenorphine's anti-depressant effect is thought to make tapering on the drug significantly more tolerable than more selective opioid agonists. Also, due to its less euphoric properties, BMT is more effective at relapse prevention than at actual drug replacement therapy (DRT). This gives the patient considerably more experience at living a seemingly "sober" life than MMT or LAAMMT, making complete abstinence a more easily achievable goal during buprenorphine therapy. As a result, BMT is usually used for a maximum of 3 years.
However, b/c buprenorphine's neurological action is different from full-opioid agonists, it is less effective as an actual alternative replacement for opioids. For this reason, individuals who aren't quite ready to stop abusing opioids respond better to methadone maintenance than to BMT.
Also, buprenorphine's antagonist properties will cause precipitated withdrawal if taken by an opioid tolerant individual who has used within 24 - 48 hours (depending what opioid was last taken). Therefore, to start BMT the patient must wait till her or she is in withdrawal to start the maintenance therapy.
From my experience: if an individual precipitates withdrawal by taking buprenorphine while on other narcotics, the symptoms can be expected to last for at least 12 hours and can not be reversed. Expect it to last at least 24 hours in severely addicted individuals. Taking other opioids or more buprenorphine will not alleviate the symptoms either. The best recommendation I can offer is to wait it out for 36 - 48 hours. Then take buprenorphine at normal doses as needed.
Propoxyphene
--------------------------------------
Being a diphenylheptane-opioid like methadone and LAAM, propoxyphene does have some anti-depressant like properties. But its disadvantages are too numerous. It has a short duration of action and weak opioid agonist activity, needing very high dosing to be effective in opioid tolerant individuals. It also has higher antagonist activity at NMDA receptors than methadone; making it less tolerated, with more side effects.
Norpropoxyphene, a metabolite of propoxyphene, is highly cardiotoxic and suspected of being neurotoxic. It has an extremely long half-life and accumulates in the body, potentially causing delayed atrioventricular conduction, psychosis, cardiac arrhythmias, circulatory impairment, impaired psychomotor function, and in some cases cardiorespiratory arrest after long periods of use. The risk of some neurocardio effects occuring immediately after one-time-use increase considerably over 800 mg.
For these reasons, propoxyphene is only effective as a short term detoxification drug. It should only be used in individuals with low to moderate tolerance due to its dangerous cardiovascular side effects.
Codeine
--------------------------------------
Codeine is an non synthetic, weak mu-opioid agonist and can be used for tapering to avoid minor withdrawal. But b/c codeine must first be converted into its active metabolite, morphine, it has a ceiling effect of 400 mg--thus it is not suitable for severe withdrawal. Also, norcodeine, another metabolite of codeine, facilitates a severe histamine reaction--another unfavorable side effect.
Tramadol
--------------------------------------
Tramadol is a synthetic opioid which is classified indepdently of all other narcotic analgesics. Tramadol is similar to codeine in that it has weak analgesic qualities. It too has a ceiling effect, but its active metabolite isn't morphine and is denoted as M1. While tramadol isn't an effective medication to relieve severe opioid cravings, it does have unique mechanisms of action that make it useful in treating other severe withdrawal symptoms: its prevention of serotonin and norepinephrine reuptake can mediate depression and its agonist activity at alpha-2 adrenergic receptors (similar to clonidine) can also relieve insomnia, fever-symptoms, and hypertension. However, tramadol can cause nausea and vomiting in higher doses and its SNRI action can leave minor yet persisting stimulation and hypertensive symptoms when taken to alleviate withdrawal.
Full Agonist Opioids: Semisynthetics (oxycodone, hydrocodone), Anilidopiperidinic derivatives (fentanyl) and Phenylpiperidinic derivatives (meperidine/pethidine)
--------------------------------------
These drugs can be effective in the short term when used for tapering. However, they are ineffective when used for long term maintenance b/c of their euphoric properties, short duration of action, and high abuse potential. Other strong mu opioid agonists like methadone, LAAM, and buprenorphine are accepted as having medical value in maintenance therapy b/c of their anti-depressant effects, limited euphoric properties, ability to block other opioids, long duration of action, and their success of use in structured, maintenance programs. Other mu-opioid agonists do not share all of these qualities. Full agonists are therefore more likely to be abused by a detoxing individual compared to other narcotic DRT medications. They are ultimately less effective in acheiving eventual sobriety unless the patient is adhered to very strict conditions and regulations, or held in a controlled environment.
Compared to typical opioids, phenylpiperidine derivatives can have added disadvantages due to their more generalized neurological effect. For example, Meperidine has strong anticholinergic activity and has some effect on kappa-opioid receptors. This can cause aggravating side effects that include: confusion, dry mouth, ataxia, hallucinations, agitation, amnesia, anesthesia, catalepsy, dysphoria, catatonia, delerium, and even psychosis. Meperdine can also precipitates stimulant effects by inhibitioning the dopamine and norepinephrine transporter cells (DAT and NAT, respectively).
NON-OPIOIDERGIC THERAPIES
Ibogaine/18-methoxycoronaridine
--------------------------------------
Ibogaine is pharamcologically unique in its relevance to treating opioid dependance. The main neurological action that is responsible for addiction surpression is noncompetitive antagonist activity at α3β4 nicotinic receptors. B/c NMDA and α3β4 nicotinic channels are located within lumen binding range on the same ligands--α3β4 nicotinic antagonism usually facilitates NMDA antagonist activity as well. In plain english: this neurological action is responsible for ibogaine's dissociative effects. This neurological action is also responsible for curbing compulsive behavior; to a lesser extent, drugs like buproprion (zyban) also have this neurological action. Ibogaine also has strong hallucinogenic and psychedelic effect, this is mediated by agonist activity at the 5HT2A receptors.
12-hydroxyibogamine, an active metabolite of ibogaine, is a selective serotonin reuptake inhibitor, and a -kappa, -mu opioid agonist. These actions are responsible for ibogaine's long duration and surpression of opioid withdrawal symptoms, respectively.
But most importantly... unlike methadone or buprenorphine, ibogaine is unique in that it actually creates a desire to become abstinent. While its nicotinergic and opioidergic effects seem to diminish mental and physical craving; its combined action on NMDA channels and 5HT2A receptors cause a deeply reflective, hallucinogenic experience in which preconcieved, positive perceptions pertaining to an individual's addiction are shattered.
Drug addiction forces an individual to rationalize one's harmful actions--its the brain's way of ignoring atypical and immoral behavior inorder to maintain use (Drug consumption to an opioid addicted brain becomes a survival skill, the brain will instinctively try to sustain it any cost). Ibogaine rips down these false, built up notions and allows the addict to see things for what they really are. This is a milestone in addiction treatment, since it was thought to be impossible to induce this in an addicted individual, i.e.- "they can only quit when they really want to." Well, now it seems most dependent users can also really quit if they take ibogaine once every few months.
Ibogaine also has some action on sigma2 receptors (a neuron-system that is involved in stimulant toxicity, anti-cholinergic delerium, and dissociative-drug induced hallucinations); but the neurological, behavorial cause and effect profile of such pharmacological actions is still poorly understood.
A synthetic derivative of iboagine is 18-methoxycoronaridine. Its neurological action is as a selective α3β4 antagonist, which is ibogaine's main mechanism for physically surpressing the compulsiveness of addiciton. But b/c it is selective, it is barely hallucinogenic and thus less intense than ibogaine. This ultimately is a major flaw in 18-methoxycoronaridine b/c it will theoritically be no more effective at mediating addiction than other selective α3β4 antagonists; it is no better than drugs like buproprion.
Naltrexone Maintenance
--------------------------------------
Naltrexone is an opioid antagonist, typically used in maintenance of sobriety in opioid dependent individuals who've already undergone detoxification. Naloxone and nalmefene are also opioid antagonists that are used to treat acute overdose and alcoholism, respectively. Naloxone has application in treating opioid overdose due to its higher potency and relatively low duration of effects (1 - 2 hrs). Nalmefene is used in alcoholism more extensively due to its low potency and high plasma half life.
Opioid antagonists have very high affinity for mu- and kappa- opioid receptors and therefore will displace any other non-competitive opioidergic drug present at the actual receptor site. This is, in essence, the pharmacodynamics of neurological antagnostic activity. Since naltrexone, naloxone, and nalmefene have no inherit mu- opioid agonist properties themselves; they will block the neurological aciton of any narcotic and cause habitual opioid users to go into precipitated withdrawal.
Naltrexone is usually prescribed following rapid detox treatment as a post procedural medication. However, the effectiveness of opioid antagonist maintenance is low due to non compliance in patients. Therefore, another procedure in which a naltrexone "pellet" is subcutaneously inserted into the patient, is sometimes utilized. The pellet has its advantages to medication b/c daily compliance in the patient is not an issue and the effects can last anywhere from 4 - 24 months.
Opioid antagonists in general are considered to be less advantageous compared to other treatment options. These drugs have absolutely no inherit opioid agonist properties, and thus do not help in treating cravings in opioid dependent individuals. Therefore, other DRT medications as a whole are considered more useful.
Rapid Detoxication
--------------------------------------
Rapid detox refers to a medical procedure used to speed up the detoxication process. Generally, the procedure can last anywhere from 30 minutes to 4 hours, depending on an individual's subjective withdrawal symptoms.
Typical medications used include a mitazolam and ketamine mixture for anesthesia, followed by high quantities of naloxone, and then nalmefene. Medicines like tracrium (a mixture of ten atracurium stereoisomers) are also sometimes used as peripherial movement inhibitors (peripherial muscle relaxants).
The effectiveness of rapid detox seems to be debated within the addiction-treatment community. For patients with high tolerance who have been using for multiple years or more, withdrawal duration can last a relatively extensive amount of time. In these cases, rapid detox seems to be less effective at condensing symptoms into a 4 hour period.
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LISTING OF PHARMACEUTICAL AND HERBAL TREATMENTS (IN ORDER FROM MOST EFFECTIVE TO LEAST EFFECTIVE)
Opioid-Based and/or Dysphoria Treating Medicines (Most of these can cause dependence):
ibogaine
methdone
buprenorphine
levoacetylmethadol (LAAM)
buspirone
oxycodone/hydrocodone
tramadol
codeine
propoxyphene
benzodiazepines
carisprodal
dextromethorphan
-------herbs-------
kratom
Non-Opioid Medications (Categorized according to symptomatic relief provided; Not dependence-prone):
Insomnia/Anxiety/Hypertension
baclofen
chlorzoxazone
cyclobenzaprine/orphenadrine
methocarbamol
zolpidem
tizanidine
amitriptyline
gabapentin
hydroxyzine
acomprosate
trazadone
dextromethorphan
clonidine
melatonin & other steroidal sleep remedies (insomnia only)
diphenhydrinate/dimenhydramine
--------herbs--------
kava kava (piper methysticum)
valerian (valeriana officinalis)
passionflower (passiflora incarnata)
reishi (ganoderma lucidum)
chamomile (matricaria recutita)
skullcap (scutellaria lateriflora)
hops (humulus lupulus)
damiana (turnera diffusa)
Diarrha/Abdominal Cramps
loperamide
amitriptyline
hydroxyzine
anticholinergics (atropine, dimenhydrinate)
------herbs------
bilberry (vaccinium myrtillus)
peppermint (mentha x piperita)
Rhinorrhea (ncreased salivation)/ Lacrimation (increased tear production)
anticholinergics
hydroxyzine
loperamide
amitriptyline
dextromethorphan
-------herbs------
belladonna alkaloids
Pyretic Sensations (chills, fever)
clonidine
propranolol
acetaminophen
NSAIDs
acetylsalicylic acid
Nausea
diphenhydramine/dimenhydrinate
meclizine
bismuth subsalicylate
hydroxyzine
calcium carbonate
------herbs------
chamomile (matricaria recutita)
ginger (zingiber officinale)
peppermint (mentha x piperita)
Aches, Pains
ropinirol
baclofen
NSAIDs (ibuprofen, naproxen)
acetaminophen
acetylsalicylic acid
chlorzoxazone
cyclobenzaprine/orphenadrine
methocarbamol
gabapentin
trazadone
------herbs------
reishi (ganoderma lucidum)
willow (salix spp.)
Non-Barbituate & Non-Benzodiazepine M03B Class Muscle Relaxants (May help with anxiety, insomnia, and pain; Some may be habit forming)
chlormezanone
tolperisone
febarbamate
phenyramidol
mephenesin
phenprobamate
styramate
thiocolchicoside
pridinol
Description and Pharmacology of Opioidergic Drug Replacement Therapies
Methadone
Levoacetylmethadol (LAAM)
Buprenorphine
Propoxyphene
Codeine
Tramadol
Full Agonist Opioids
Description and Pharmacology of Non-Opioidergic Therapies
Ibogaine/18-methoxycoronaridine
Naltrexone Maintenance
Rapid Detoxification
Listing of Pharmaceutical and Herbal Treatments for Withdrawal
Opioid Based Medicines (For treatment of dysphoria)
Non-Opioid Based Medicines (Classified by the symptomatic relief they provide; Generally non-dependence prone)
-Insomnia/Anxiety/Hypertension
-Diarrha/Abdominal Cramping
-Rhinorrhea (Increased salivation)/Lacrimation (Increased tear production)
-Pyretic Sensations (Chills, fever)
-Nausea
-Aches, Pains
Non-Barbituate & Non-Benzodiazepine M03B Class Muscle Relaxants (May help with anxiety, insomnia, and pain; Some may be habit forming)
--------------------------------------------------------------------------------------------------
OPIOIDERGIC DRUG REPLACEMENT THERAPIES
Methadone
--------------------------------------
Methadone is a diphenylheptane-derivative, a potent mu-agonist opioid, and both an effective treatment for narcotic addiction and pain. Its duration of action is quite long, lasting anywhere from 12 - 36 hours, based on dosage. It has similar risks to that of traditional opioid narcotics regarding dependency, tolerance, and withdrawal. However, b/c longer acting drugs take longer to metabolize; less drug is introduced during a given interval of time--the result is a longer retained but less intense psychoactive effect. An example of this: dia-morphine (heroin) is metabolized more quickly than morphine due to its attatched diactyl-group; the result is heroin's shorter duration in action but more intense effects, producing more euphoria and a stronger rush.
Methdone also has a unique pharmacological action in having minor, non-competitive antagonist activity at NMDA receptors, similar to but weaker than drugs like dextromethorphan and ketamine. In a small percentage of people this can facilitate a varied response of unwanted side effects including: amnesia, catalepsy (sensation of rigid muscles), confusion, dysphoria, agitation, ataxia, and/or catatonia.
However, methadone is also is a weak inhibitor of serotonin and norepinephrine reuptake. These properties give methadone an added benefit of being a minor anti-depressant. But because hypertension associated with withdrawal is attributed to elevated norepinephrine levels, methadone's SNRI activity can cause persisting, residual stimulation and hypertensive symptoms for a few days if MRT is started after a bout of withdrawal.
Methadone does have an added benefit of a blocking other opioids at and around 70 mg. Methadone isn't a competitive agonist, so it will not completely block other mu-agonists or precipitate withdrawal. This exact mechanism of blocking isn't known, but is sometimes attributed, and controversly so, to the fact that there is usually a ceiling effect on the euphoria and analgesia caused by most opioids that attain their primary psychoactive action from the activity of their corresponding metabolites. And b/c only so much of a certain molecule can be converted into a metabolite at once, a ceiling effect comes into play. But drugs which are active in themselves are still blocked to some degree by methadone. Other theories involving a maximum limit on immediate mu agonism are proposed but have no significant scientific evidence to date.
Unfortunately, withdrawal from methadone is notoriously unpleasant. If not tapered correctly, withdrawal and extreme discomfort can last up to 1 - 4 weeks. But even when done properly it can cause malaise-conditions (dysphoria associated with drug use) for 3 - 10 days. This disadvantage in MMT withdrawal can potentially instigate a relapse.
Also, there has been one reported case of death from methadone withdrawal (>175 mg daily intake). The victim died from complications during episodes of seizuring. But due to her unfortunate circumstances it was not known whether she was previously epileptic (she was incarcerated and had no known family or doctors to contact for medical information); thus it can not be definitively concluded if her death was directly due to methadone withdrawal or epilepsy complications.
So generally speaking, methadone is more effective as a long term DRT maintenance medication due to its full mu-opioid agonist pharmacology. It can cause euphoria and has relatively high abuse potential, but when used properly these effects can be minimized. But methadone can still contribute to complications when tapering b/c of its similarity in action to typical narcotic analgesics. Therefore, methadone maintenance is more suited towards substituting, regulating, and minimizing illicit opioid addiction rather than promoting eventual abstinence. Experimental, case-study evidence for this can be found at http://opioids.com/methadone/tapering.html.
Levoacetylmethadol (LAAM)
--------------------------------------
LAAM is also a diphenylheptane-derivative, like methadone and propoxyphene. Its risks and benefits are nearly identical to that of methadone's but with one major difference. LAAM's duration of action is roughly double that of its counterpart and only requires dosing 3 - 4 times a week. Generally though, it is less favored to methadone (i tend to agree) b/c of its tendency to take longer to relieve withdrawal.
Recently, LAAM's metabolites have shown signs of cardiotoxicity at normal maintenance doses, therefore it has since been discontinued for medical use in the U.S. but is still available in MMT clinics. There are also suspicions of hepatoxicity being caused by LAAMMT as well. Its dextro isomer has shown less toxicity but has significantly less duration of action and more abuse-potential; methadone is more appropriate if LAAM isn't well tolerated.
Buprenorphine
--------------------------------------
Buprenorphine belongs to a small group of opioids known as benzomorphane derivatives. Buprenorphine is a novel medication b/c it has both mu-opioid agonist and antagonist properties. It is highly competitve at receptor sites, making it similar to nalaxone and naltrexone. But unlike these drugs, it also has an inherit mu-opioid agonist effect. It produces typical narcotic analgesia at lower doses and can ward off withdrawal for up to 48 hours.
Buprenorphine's competitive affinity for opioid receptors means that it has an advantage in the fact that full-opioid agonists will have no neurological action when taken during maintenance therapy. However, at amounts less than 2 mg this effect is less pronounced and wears off 12 - 24 hours after last dose.
Because buprenorphine is not a full mu-opioid agonist, it has a ceiling limit on its effects. Over 8 - 16 mg, the analgesic and euphoric properties do not increase; only duration in action is extended. Also, buprenorphine's unique pharmacological profile means that once BMT is mantained for a few weeks euphoria, sedation, and the potential for abuse becomes of relatively less significance.
Buprenorphine also has action at the ORL1 nociceptin (a newly discovered opioid receptor-class) receptors as a partial agonist and antagonist. In low doses, this can result in novel anti-depressant like effect; but when sudden, higher doses are used during maintenance therapy, this can result in lethargy, sedation, and mild dysphoria. This has an added detering effect in patients seeking to abuse buprenorphine when in maintenance therapy.
Buprenorphine's anti-depressant effect is thought to make tapering on the drug significantly more tolerable than more selective opioid agonists. Also, due to its less euphoric properties, BMT is more effective at relapse prevention than at actual drug replacement therapy (DRT). This gives the patient considerably more experience at living a seemingly "sober" life than MMT or LAAMMT, making complete abstinence a more easily achievable goal during buprenorphine therapy. As a result, BMT is usually used for a maximum of 3 years.
However, b/c buprenorphine's neurological action is different from full-opioid agonists, it is less effective as an actual alternative replacement for opioids. For this reason, individuals who aren't quite ready to stop abusing opioids respond better to methadone maintenance than to BMT.
Also, buprenorphine's antagonist properties will cause precipitated withdrawal if taken by an opioid tolerant individual who has used within 24 - 48 hours (depending what opioid was last taken). Therefore, to start BMT the patient must wait till her or she is in withdrawal to start the maintenance therapy.
From my experience: if an individual precipitates withdrawal by taking buprenorphine while on other narcotics, the symptoms can be expected to last for at least 12 hours and can not be reversed. Expect it to last at least 24 hours in severely addicted individuals. Taking other opioids or more buprenorphine will not alleviate the symptoms either. The best recommendation I can offer is to wait it out for 36 - 48 hours. Then take buprenorphine at normal doses as needed.
Propoxyphene
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Being a diphenylheptane-opioid like methadone and LAAM, propoxyphene does have some anti-depressant like properties. But its disadvantages are too numerous. It has a short duration of action and weak opioid agonist activity, needing very high dosing to be effective in opioid tolerant individuals. It also has higher antagonist activity at NMDA receptors than methadone; making it less tolerated, with more side effects.
Norpropoxyphene, a metabolite of propoxyphene, is highly cardiotoxic and suspected of being neurotoxic. It has an extremely long half-life and accumulates in the body, potentially causing delayed atrioventricular conduction, psychosis, cardiac arrhythmias, circulatory impairment, impaired psychomotor function, and in some cases cardiorespiratory arrest after long periods of use. The risk of some neurocardio effects occuring immediately after one-time-use increase considerably over 800 mg.
For these reasons, propoxyphene is only effective as a short term detoxification drug. It should only be used in individuals with low to moderate tolerance due to its dangerous cardiovascular side effects.
Codeine
--------------------------------------
Codeine is an non synthetic, weak mu-opioid agonist and can be used for tapering to avoid minor withdrawal. But b/c codeine must first be converted into its active metabolite, morphine, it has a ceiling effect of 400 mg--thus it is not suitable for severe withdrawal. Also, norcodeine, another metabolite of codeine, facilitates a severe histamine reaction--another unfavorable side effect.
Tramadol
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Tramadol is a synthetic opioid which is classified indepdently of all other narcotic analgesics. Tramadol is similar to codeine in that it has weak analgesic qualities. It too has a ceiling effect, but its active metabolite isn't morphine and is denoted as M1. While tramadol isn't an effective medication to relieve severe opioid cravings, it does have unique mechanisms of action that make it useful in treating other severe withdrawal symptoms: its prevention of serotonin and norepinephrine reuptake can mediate depression and its agonist activity at alpha-2 adrenergic receptors (similar to clonidine) can also relieve insomnia, fever-symptoms, and hypertension. However, tramadol can cause nausea and vomiting in higher doses and its SNRI action can leave minor yet persisting stimulation and hypertensive symptoms when taken to alleviate withdrawal.
Full Agonist Opioids: Semisynthetics (oxycodone, hydrocodone), Anilidopiperidinic derivatives (fentanyl) and Phenylpiperidinic derivatives (meperidine/pethidine)
--------------------------------------
These drugs can be effective in the short term when used for tapering. However, they are ineffective when used for long term maintenance b/c of their euphoric properties, short duration of action, and high abuse potential. Other strong mu opioid agonists like methadone, LAAM, and buprenorphine are accepted as having medical value in maintenance therapy b/c of their anti-depressant effects, limited euphoric properties, ability to block other opioids, long duration of action, and their success of use in structured, maintenance programs. Other mu-opioid agonists do not share all of these qualities. Full agonists are therefore more likely to be abused by a detoxing individual compared to other narcotic DRT medications. They are ultimately less effective in acheiving eventual sobriety unless the patient is adhered to very strict conditions and regulations, or held in a controlled environment.
Compared to typical opioids, phenylpiperidine derivatives can have added disadvantages due to their more generalized neurological effect. For example, Meperidine has strong anticholinergic activity and has some effect on kappa-opioid receptors. This can cause aggravating side effects that include: confusion, dry mouth, ataxia, hallucinations, agitation, amnesia, anesthesia, catalepsy, dysphoria, catatonia, delerium, and even psychosis. Meperdine can also precipitates stimulant effects by inhibitioning the dopamine and norepinephrine transporter cells (DAT and NAT, respectively).
NON-OPIOIDERGIC THERAPIES
Ibogaine/18-methoxycoronaridine
--------------------------------------
Ibogaine is pharamcologically unique in its relevance to treating opioid dependance. The main neurological action that is responsible for addiction surpression is noncompetitive antagonist activity at α3β4 nicotinic receptors. B/c NMDA and α3β4 nicotinic channels are located within lumen binding range on the same ligands--α3β4 nicotinic antagonism usually facilitates NMDA antagonist activity as well. In plain english: this neurological action is responsible for ibogaine's dissociative effects. This neurological action is also responsible for curbing compulsive behavior; to a lesser extent, drugs like buproprion (zyban) also have this neurological action. Ibogaine also has strong hallucinogenic and psychedelic effect, this is mediated by agonist activity at the 5HT2A receptors.
12-hydroxyibogamine, an active metabolite of ibogaine, is a selective serotonin reuptake inhibitor, and a -kappa, -mu opioid agonist. These actions are responsible for ibogaine's long duration and surpression of opioid withdrawal symptoms, respectively.
But most importantly... unlike methadone or buprenorphine, ibogaine is unique in that it actually creates a desire to become abstinent. While its nicotinergic and opioidergic effects seem to diminish mental and physical craving; its combined action on NMDA channels and 5HT2A receptors cause a deeply reflective, hallucinogenic experience in which preconcieved, positive perceptions pertaining to an individual's addiction are shattered.
Drug addiction forces an individual to rationalize one's harmful actions--its the brain's way of ignoring atypical and immoral behavior inorder to maintain use (Drug consumption to an opioid addicted brain becomes a survival skill, the brain will instinctively try to sustain it any cost). Ibogaine rips down these false, built up notions and allows the addict to see things for what they really are. This is a milestone in addiction treatment, since it was thought to be impossible to induce this in an addicted individual, i.e.- "they can only quit when they really want to." Well, now it seems most dependent users can also really quit if they take ibogaine once every few months.
Ibogaine also has some action on sigma2 receptors (a neuron-system that is involved in stimulant toxicity, anti-cholinergic delerium, and dissociative-drug induced hallucinations); but the neurological, behavorial cause and effect profile of such pharmacological actions is still poorly understood.
A synthetic derivative of iboagine is 18-methoxycoronaridine. Its neurological action is as a selective α3β4 antagonist, which is ibogaine's main mechanism for physically surpressing the compulsiveness of addiciton. But b/c it is selective, it is barely hallucinogenic and thus less intense than ibogaine. This ultimately is a major flaw in 18-methoxycoronaridine b/c it will theoritically be no more effective at mediating addiction than other selective α3β4 antagonists; it is no better than drugs like buproprion.
Naltrexone Maintenance
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Naltrexone is an opioid antagonist, typically used in maintenance of sobriety in opioid dependent individuals who've already undergone detoxification. Naloxone and nalmefene are also opioid antagonists that are used to treat acute overdose and alcoholism, respectively. Naloxone has application in treating opioid overdose due to its higher potency and relatively low duration of effects (1 - 2 hrs). Nalmefene is used in alcoholism more extensively due to its low potency and high plasma half life.
Opioid antagonists have very high affinity for mu- and kappa- opioid receptors and therefore will displace any other non-competitive opioidergic drug present at the actual receptor site. This is, in essence, the pharmacodynamics of neurological antagnostic activity. Since naltrexone, naloxone, and nalmefene have no inherit mu- opioid agonist properties themselves; they will block the neurological aciton of any narcotic and cause habitual opioid users to go into precipitated withdrawal.
Naltrexone is usually prescribed following rapid detox treatment as a post procedural medication. However, the effectiveness of opioid antagonist maintenance is low due to non compliance in patients. Therefore, another procedure in which a naltrexone "pellet" is subcutaneously inserted into the patient, is sometimes utilized. The pellet has its advantages to medication b/c daily compliance in the patient is not an issue and the effects can last anywhere from 4 - 24 months.
Opioid antagonists in general are considered to be less advantageous compared to other treatment options. These drugs have absolutely no inherit opioid agonist properties, and thus do not help in treating cravings in opioid dependent individuals. Therefore, other DRT medications as a whole are considered more useful.
Rapid Detoxication
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Rapid detox refers to a medical procedure used to speed up the detoxication process. Generally, the procedure can last anywhere from 30 minutes to 4 hours, depending on an individual's subjective withdrawal symptoms.
Typical medications used include a mitazolam and ketamine mixture for anesthesia, followed by high quantities of naloxone, and then nalmefene. Medicines like tracrium (a mixture of ten atracurium stereoisomers) are also sometimes used as peripherial movement inhibitors (peripherial muscle relaxants).
The effectiveness of rapid detox seems to be debated within the addiction-treatment community. For patients with high tolerance who have been using for multiple years or more, withdrawal duration can last a relatively extensive amount of time. In these cases, rapid detox seems to be less effective at condensing symptoms into a 4 hour period.
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LISTING OF PHARMACEUTICAL AND HERBAL TREATMENTS (IN ORDER FROM MOST EFFECTIVE TO LEAST EFFECTIVE)
Opioid-Based and/or Dysphoria Treating Medicines (Most of these can cause dependence):
ibogaine
methdone
buprenorphine
levoacetylmethadol (LAAM)
buspirone
oxycodone/hydrocodone
tramadol
codeine
propoxyphene
benzodiazepines
carisprodal
dextromethorphan
-------herbs-------
kratom
Non-Opioid Medications (Categorized according to symptomatic relief provided; Not dependence-prone):
Insomnia/Anxiety/Hypertension
baclofen
chlorzoxazone
cyclobenzaprine/orphenadrine
methocarbamol
zolpidem
tizanidine
amitriptyline
gabapentin
hydroxyzine
acomprosate
trazadone
dextromethorphan
clonidine
melatonin & other steroidal sleep remedies (insomnia only)
diphenhydrinate/dimenhydramine
--------herbs--------
kava kava (piper methysticum)
valerian (valeriana officinalis)
passionflower (passiflora incarnata)
reishi (ganoderma lucidum)
chamomile (matricaria recutita)
skullcap (scutellaria lateriflora)
hops (humulus lupulus)
damiana (turnera diffusa)
Diarrha/Abdominal Cramps
loperamide
amitriptyline
hydroxyzine
anticholinergics (atropine, dimenhydrinate)
------herbs------
bilberry (vaccinium myrtillus)
peppermint (mentha x piperita)
Rhinorrhea (ncreased salivation)/ Lacrimation (increased tear production)
anticholinergics
hydroxyzine
loperamide
amitriptyline
dextromethorphan
-------herbs------
belladonna alkaloids
Pyretic Sensations (chills, fever)
clonidine
propranolol
acetaminophen
NSAIDs
acetylsalicylic acid
Nausea
diphenhydramine/dimenhydrinate
meclizine
bismuth subsalicylate
hydroxyzine
calcium carbonate
------herbs------
chamomile (matricaria recutita)
ginger (zingiber officinale)
peppermint (mentha x piperita)
Aches, Pains
ropinirol
baclofen
NSAIDs (ibuprofen, naproxen)
acetaminophen
acetylsalicylic acid
chlorzoxazone
cyclobenzaprine/orphenadrine
methocarbamol
gabapentin
trazadone
------herbs------
reishi (ganoderma lucidum)
willow (salix spp.)
Non-Barbituate & Non-Benzodiazepine M03B Class Muscle Relaxants (May help with anxiety, insomnia, and pain; Some may be habit forming)
chlormezanone
tolperisone
febarbamate
phenyramidol
mephenesin
phenprobamate
styramate
thiocolchicoside
pridinol
Last edited:
AlphaOdure
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If anyone has any comments or anything to add... please do so.
AlphaOdure
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^ ^ ^
Huh? I'm not following you??
Huh? I'm not following you??
AlphaOdure
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^ ^ ^
Huh? I'm not following you?
Quit what? Trying to help people w/ withdrawal? Or were you referring to my personal drug use? B/c if you were, then you should also have observed from my posts that i don't use any drugs; unless you count my Rx to suboxone.
Huh? I'm not following you?
Quit what? Trying to help people w/ withdrawal? Or were you referring to my personal drug use? B/c if you were, then you should also have observed from my posts that i don't use any drugs; unless you count my Rx to suboxone.
AlphaOdure
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zophen said:
Since both methadone and ketamine are non competitive antagonists at NMDA receptors (obviously ketamine having more activity there)--hypothetically, they wont literally block one another, like naloxone would heroin. However... although I am not as familar with the pharmacodynamics of glutamte and NMDA receptors systems, i am pretty sure second-dosing metabolism is very ineffective.
Meaning.... just how redosing K a few minutes after you've just taken it wont work; so too would be the case when taking K 12 - 24 hours after dosing methadone or LAAM. Hypothetically, propoxyphene would block it as well.
Or so it logically seems.
zophen said:
Makes sense. No need for an apology... if it makes you feel any better.. i really wasn't offended b/c i couldn't understand what the hell kind of point you were trying to make. But now i see it was just incoherent ketamine babble. haha
AlphaOdure
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^ ^ ^
Damn dude you must be fucked up, ha! I explained in my post... what i meant by that was, neurologically they wouldn't block one another like competitive antagonists would, like naloxone and heroin. But the blocking mechanism you experienced was probably due to rapid tolerance build up... i.e.- how you can't get any strong effect out of redosing dissociatives in rapid sequence; the same could be true of taking dissociatives after dosing any sort of diphenylheptane opioid.
what i posted...
Damn dude you must be fucked up, ha! I explained in my post... what i meant by that was, neurologically they wouldn't block one another like competitive antagonists would, like naloxone and heroin. But the blocking mechanism you experienced was probably due to rapid tolerance build up... i.e.- how you can't get any strong effect out of redosing dissociatives in rapid sequence; the same could be true of taking dissociatives after dosing any sort of diphenylheptane opioid.
what i posted...
AlphaOdure
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BTW, that sucks. what a waste of ketamine.
Did it take 4 months of complete abstinence from methadone to get any effect? If so, that could imply mild glutamate neurotoxicty from diphenylheptane opioids.
Did it take 4 months of complete abstinence from methadone to get any effect? If so, that could imply mild glutamate neurotoxicty from diphenylheptane opioids.
AlphaOdure
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mwhahahahaha; yeaa thats a good topic to take up over there.
but i like to post in TDS b/c of the recovery orientated atmosphere here. I know, my pharmacological mumbo jumbo can get sort of confusing and annoying at times though.
In plain english.. what i meant by that question was... did it take you 4 months after stopping methadone to get any effect from ketamine? If it did, that means methadone may do some lasting damage to glutamate receptors.
but i like to post in TDS b/c of the recovery orientated atmosphere here. I know, my pharmacological mumbo jumbo can get sort of confusing and annoying at times though.
In plain english.. what i meant by that question was... did it take you 4 months after stopping methadone to get any effect from ketamine? If it did, that means methadone may do some lasting damage to glutamate receptors.
Don't worry man, I'm enjoying the pharmcology 'mumbo jumbo' 
I'm quite interested in pharmacology but unfortunately fucked up my year 12 with too many drugs and didn't get the marks I need to get into the pharmacology course.
Very interesting read, from my own personal experience, your points on buprenorphine are completely valid. I get almost no high, or really any effects at all, it simply keeps me from withdrawing - therefore allowing me to lead a normal life.
Thanks for going to all the time and effort to do this, will make a very useful resource.
I'm quite interested in pharmacology but unfortunately fucked up my year 12 with too many drugs and didn't get the marks I need to get into the pharmacology course.Very interesting read, from my own personal experience, your points on buprenorphine are completely valid. I get almost no high, or really any effects at all, it simply keeps me from withdrawing - therefore allowing me to lead a normal life.
Thanks for going to all the time and effort to do this, will make a very useful resource.