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Opioids Tramadol MEGATHREAD and ESSENTIAL&SIMPLE information about it.

Jabberwocky

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TRAMADOL MEGATHREAD


1. What is Tramadol ?
2. Pharmacology of Tramadol.
3. The two main characteristcs and ways of action.
4. Routes of administration and bioavailability.
5. Side effects.
6. Withdrawal.
7. Potentiation.
8. Interaction with other medicines and other forms of interaction.


1. What is Tramadol?

Tramadol is an opioid pain medication used to treat moderate to moderately severe pain.

Tramadol is a fully synthetic opioid unlike opiates like Morphine or Codeine which are found in the poppy plant ( Papaverus Somniferum ) or semi-synthethic opioids like Diamorphine (Heroin) .


Tramadol acts by binding to the μ-opioid receptor of the neuron and is also a serotonin–norepinephrine reuptake inhibitor.


Beside the medical uses, it has recreational uses with similar and also unique characteristics as other opioids.


It's usage is mainly limited by the lowered seizure threshold or defficiency of the CYP2D6 enzyme.


2. Pharmacology of Tramadol


Tramadol itself is not as active as you would believe and the binding affinity of the substance itself is lower than those of its metabolites.

The metabolism of tramadol is liver-mediated demethylation and glucuronidation via CYP2D6 & CYP3A4.

The two active metabolites resulted are desmetramadol (O-desmethyltramadol), which is the major active metabolite, and nortramadol which adds to its uniqueness compared to other opiates/opioids due to the amplified SNRI/SRI activity it has.

Tramadol acts on the opioid receptors through its major active metabolite desmetramadol, which has as much as 700-fold higher affinity for the MOR relative to tramadol. Moreover, tramadol itself has been found to possess no efficacy in activating the MOR in functional activity assays, whereas desmetramadol activates the receptor with high intrinsic activity (Emax equal to that of morphine). As such, desmetramadol is exclusively responsible for the opioid effects of tramadol.


Other properties:
Agonist of the μ-opioid receptor (MOR) and to a far lesser extent of the δ-opioid receptor (DOR) and κ- opioid receptor (KOR)
Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor); hence, an SNRI
Serotonin 5-HT2C receptor antagonist
M1 and M3 muscarinic acetylcholine receptor antagonist
α7 nicotinic acetylcholine receptor antagonist
NMDA receptor antagonist (very weak)
TRPA1 inhibitor


The difference in the affinity is not the only one, as the halflife of Tramadol has an aprox value of 6 hours while desmetramadol aprox. 9 hours. ( PLEASE TAKE IN CONSIDERATION THAT THIS VARRIES FROM PERSON TO PERSON, AND FROM INSTANT RELEASE TO EXTENDED RELEASE, AS SOME OF YOU MIGHT TAKE OTHER MEDICATION CONTRAINDICATED IN COMBINATION OF TRAMADOL PLEASE DON'T TAKE THESE HALF LIFE VALUES FOR GRANTED AND CONSULT YOUR DOCTOR ).


3. The two main ways of action.


Normally this subject would be and is partially covered in the Pharmacology section.

But considering that some of you use it in self medicating purposes which are not related to pain and don't know why it has such a "positive" (this is subjective) effect on your mood, it will be covered shortly.
So we all know that the main action of it is in its opioid-like properties, but due to the SNRI/SRI activity it has an antidepressant, anti-anxiety and mood enhancing activity. It tends to be more prominent than in other opiates and feel kinda weird that's why people describe the "high"/effect dirty.


Although it is structurally similar to Effexor and other such compounds I advise against using it as an antidepressant due to the seizure risk, double withdrawal ( beside the SNRI withdrawal you will feel the main part of its withrawal arsenal which is very opiate/semi-syntethic opioid/fully syntethic opioid like ).

So if you hate the brain zaps, mood swings and enhanced angryness avoid!


Another short note which is not fully medically sustained but by my own experience, some psyhiatrist tend to misdiagnose tramadol addicts with bipolar disorder, had couple of friends diagnosed with it when they went to rehab because of tramadol and I assure you they are not bipolar at all, compared to legit bipolar people I also know. My guess would be the cause of this misdiagnose is due to the major mood swings experienced at high dosages or in tramadol withdrawal.


4. Routes of administration, bioavailability and dosage.


Dosage:


BIG WARNING: Tramadol causes seizures, saw a lot of them at low doses, mid doses, high doses so please take caution, if you are predisposed please use another opioid/opiate or seek an alternative treatment approved by your doctor.

The maximum dosage per day approved by doctors would be 400mg per day.

For a begginer I would suggest starting with 100 mg and add 50 mg until you reach the level you want,
it has excelent re-dosing potential unlike other substances ( for example codeine which has a ceiling effect and re-dosing can be tricky without the ceiling also.


BIGGEST LESSON LEARNED HERE ON BLUELIGHT: YOU CAN ALWAYS AND MORE BUT YOU CAN'T DROP THE DOSAGE AFTER YOU TOOK IT. JUST LIKE WITH SALT ADDED TO FOOD.


The effects with the immediate release formula can kick in between 30-45 minutes while the extend ones start to kick in between 1-3 hours. So before re-dosing please consider this.


WARNING: If you have a formulation that includes something else than Tramadol too, like Ultram which has APAP or here in Romania Dorretta, please consider doing a cold water extraction exactly like when you do with codeine and APAP products, the solubility varies but the tramadol already does some damage and combined with APAP it is rough on the liver.


Routes of administration and biovailability:


Oral: 70% to 75%


This is the ROA I recommend the most due to the liver-mediated demethylation talked about in section 2, the simplicity of the administration and the less risks associated with it ( for example: IV has lots of risks like infections, abscesses etc.)

Rectal: 77%


This ROA can be done by plugging or suppositories sold by pharmacies.
For details about plugging substances please search for the plugging thread through the search engine located in the upper left corner of the forum or on google by typing site::bluelight.com after the keyword.


IM: 100%


For this ROA please use ampoules (vials) directly bought from the pharmacy, IM''ing pills is even more dangerous than IV'ing them as the binders and fillers get stuck in the tissue and can cause an abcess.


IV: 100 %


As for the IM ROA vials must be used too and not pills ( it does not matter if they are legit, pressed, instant release or extended release, IV'ing pills is a plain NO NO. )



5. Side Effects.


Its properties of lowering the seizure threshold are the biggest risk factor.

Chemical unbalance in the brain is another one which can result in depression, anxiety, mood swings, angryness etc. ( so don't be fooled by its antidepressant properties as those can take a big U Turn and surprise you)


The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness, and headache. Compared to other opioids, respiratory depression and constipation are considered less of a problem with tramadol.


Another big one would be the addiction potential, some doctors might say that is less addictive than other opioids or not at all, well this is not true at all as I've been addicted to it for 6 years + and even prefered it over morphine, oxycodone, fentanyl, codeine etc. Even when I would use one of the substances stated I would always use tramadol also that''s how addictive it can be . ( please don't take other opioids or benzos with tramadol it won't become more magical than it is, only the side effects become more "magical" ).


Avoid using it in combination with MAOis and other SNRI, SRI substances, if you are so desperate to due so please ask about this issue the psychiatrist that prescribed you the MAOI/SNRI/SRI.


6. Withdrawal.


Now this is a very unique part of it, as I said in other sections it is an opioid and SNRI/SRI working substance so the withdrawal will always have dual properties, that's why I for example found it hard to quit because the SNRI/SRI part would result in brain zaps, mood swings and crippling depression/anxiety.


Combine the withdrawal symptoms from above with the typical ones resulted from other opiod withdrawals nausea, diarheea , stomach pain, muscle pain, insomnia and restless leg syndrome and it will result in a typical tramadol withdrawal.


The addiction can be stopped by two ways of quitting : Cold Turkey ( you stop taking it all at once ) or tappering where you titrate the dosage by an amount which you found comfortable.


Real life example: I was addicted to a huge dosage between 1000-1500 mg which is stupidly dangerous and would do big damage to anyone without a tolerance and even with one (don't think that cross- tolerance works as between oxy and morphine for example due to the nortramadol thing).

My tappering plan ( APPROVED BY A PSYCHIATRIST ) was to go 100mg down per week so this kind of tappering in my case took about 10-11 weeks.


Withdrawal can be defeated in Cold Turkey with OTC medications such as Immodiun, Non-Steroidal Anti-Inflamatorry Drugs as ie. Ibuprofen, benzos ( I advise against benzos due to their abuse and addiction potential, but if you find yourself having seizures which is possible in tramadol withdrawal I would recommend taking them but only after consulting your DOCTOR as I am not qualified as one by any degree).


7.Potentiation


Tramadol can be potentiated by :
Nicotine
Caffeine
Grapefruit Juice
Other CY2PD6 enzyme function enhancers beside Grapefruit Juice.
Benzos ( Not a big difference, I would take them only at mega high doses to prevent seizures)
Other Opiates/Opiods (If you are in position to do this, just switch to a stronger opiate you feel comfortable with as the respiraty depression can become more prevalent than with using only tramado, plus it's good to avoid a double opiate additction as I had for some time).


FINAL NOTES:
This megathread was created due to frequently asked questions about tramadol usage, I'm no chemist, doctor or anything related, just had a long love affair with it as a kid and big curiosities about psyhoactive substances, all these elements resulting in my knowledge.


Any modifications, edits, additional knowledge are welcomed.

KK edit:

8. Interaction with other medicines and other forms of interaction.
Copied from https://www.medsafe.govt.nz/profs/Datasheet/t/TramalcapSRtabinjoraldrops.pdf

Use with Benzodiazepines and other Central Nervous System (CNS) Depressants:
Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS-depressants including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.

Tramadol should be used with caution and in reduced dosages when administered to patients receiving Benzodiazepines and CNS-depressants such as sedative/hypnotics, anxiolytics, tranquillisers, muscle relaxants, general anaesthetics, drugs with antihistaminesedating actions such as antipsychotics, phenothiazines, alcohol, other opioids.

The combination of tramadol with mixed opiate agonists/antagonists (eg. buprenorphine, pentazocine) is not advisable because the analgesic effect of a pure agonist may be theoretically reduced in such circumstances.

Use with other serotonergic agents:
The presence of another drug that increases serotonin by any mechanism should alert the treating physician to the possibility of aninteraction.
Concomitant therapeutic use of tramadol and serotonergic medicines such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors
(SNRIs), MAO inhibitors (see 4.3 Contraindications), tricyclic antidepressants and mirtazapine may cause serotonin toxicity. Serotonin syndrome is likely when one of the
following is observed:
- Spontaneous clonus
- Inducible or ocular clonus with agitation or diaphoresis
- Tremor and hyperreflexia
- Hypertonia and body temperature >38?C
Check out this thread for more information on Serotonin Syndrome/Serotonin toxicity

Use with coumarin derivatives -> caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (eg. warfarin) due to reports of increasedinternational normalised ratio (INR) with major bleeding and ecchymoses in some patients.

Drugs which reduce the seizure threshold -> tramadol can induce convulsions and increase the potential for selective serotonin re-uptake inhibitors(SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other seizure threshold lowering agents (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions.

Use with MAO inhibitors -> tramadol should not be used in patients who are taking MAO inhibitors or who have taken them within the last fourteen days, as tramadol inhibits the uptake of noradrenaline and serotonin.

Concomitant administration of tramadol with carbamazepine causes a significant increase in tramadol metabolism, presumably through metabolic induction by carbamazepine.

Tramadol is metabolised to M1 by the CYP2D6 P450 isoenzyme. Drugs that selectively inhibit that isoenzyme (quinidine, phenothiazines, antipsychotic agents) may cause increased concentrations of tramadol and decreased concentrations of M1.

Concomitant administration of tramadol with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics.

Other drugs known to inhibit the CYP3A4 isoenzyme of cytochrome P450, such as ketoconazole and erythromycin, may inhibit the metabolism of tramadol (via Ndemethylation) and probably the metabolism of the active O-demethylated metabolite (M1). The clinical importance of such an interaction has not been studied.
 
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Jabberwocky

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No problem ! Planned to do this about 1 year ago but ironically wrote this after I quit, I am past the acute withdrawal phase and 10 days clean but I am still fascinated by it.
 

apple456tgb

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Great post, great information. As far as potenation, whenever I take Benzo + Tramadol, usually valium, always seems to over power the Tramadol effects and I feel more relaxed than euphoric, so I would advise against Benzo + Tramadol, but thats just me. Also must say Valium may have saved me a couple times on 500mg+ doses of tramadol where I start shaking and might be close to seizure but I take valium to calm down so Benzos can be life saving.
 

Jabberwocky

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Yes you are right, in my case too. though my choice was usually clonazepam (rivotril) but mixed it with valium and other benzos also. In my opion as you said only for the seizure preventing purposes are the benzos viable, plus if you become addicted to both you risk even more chance of a seizure as benzo and tramadol withdrawal can both cause it.

A friend almost died in highschool once as he took 500mg as I used to in that period without telling me even after I told him that 100-150 mg is more than enough. He had a seizure in class, his lungs stopped, his heart stopped and he needed to be resuscitated. He was very lucky that a person in the class knew first aid techniques as he voluntered in some non-profit organization.
 

zagor11

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I am getting off oxy and using gabapentin, tramadol, clonidin, kratom, plus I am on a few AD including dexedrine. Someone said not to use TRAMADOL with kratom and dexedrine. I don't think clonidine does a shit at recommended dose 0.3 mg. I have been using mostly gabapentin and im getting addicted on it.

Tramadol and Kratom cannot give me any buzz cuz im "high-free" due to tolerance.
 

Jabberwocky

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thank you! at section 5 at side effects I wrote that people should avoid combining them with MAOIs and other snri/srri, just it was added after I edited it a couple of times.

I've only experienced it with valdoxxan and effexor ( seroquel also but that is mainly an anti-psyhotic ) when I got out of rehab and relapsed while still on the treatment. but if you want I can add a separate interactions section as I did read a lot of studies on ncib and such sites beside personal experience.

PS:

I am really glad that I could help on these forums , it's a veeeery small gift from me considering all the helping you guys did over the time period I posted on these forums. Even on things I have mid to high level knowledge I made a habbit of checking out what is said on bluelight in several threads. When I was a teen erowid was everything for me but it lacked the community this place has.
 

Jabberwocky

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not at all, I would have one question also.

I still have muscle spams beside brain zaps (been clean for 10 days, tonight would be the 11th) are this permanent?

I used to have more frecvent ones in the past while on mega doses and started to have less with tapering, I have read that brain zaps are not dangerous but the muscle spams thing makes me anxious, mainly about it evolving in something worse. My first psychiatrist when I was a teen said that due to prolonged use I may become affected by huntington disease and that was like 5 years ago, so idk if she was trying to scare me as I was younger or it may develop.
 

kleinerkiffer

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Have you tried a magnesium supplement for the muscle spasms?

And regarding Huntington disease, it's typically hederitary, meaning that you have to inherit it from your parents (sometimes the mutation causing it developes later in life, but it's highly unlikely).

Brain zaps/shivers seem to still be a poorly understood symptom of antidepressant/tramadol withdrawal.
Looking at this case report it may be caused by a norepinephrine imbalance
Since the “brain shivers” were the most distressing symptom, a trial of atomoxetine 40 mg/d was attempted based on the hypothesis that the symptom was a result of noradrenergic imbalance.9 An immediate improvement in “brain shivers” was reported within 2 or 3 hours of taking the first dose.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733524/
Maybe taking low dose atomoxetine and slowly tappering it might help?

Looking at this it might take a long time until the brain zaps subside, I guess only time will tell:
110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023).
https://www.ncbi.nlm.nih.gov/pubmed/29758951
 

Jabberwocky

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thanks for all the info kk! I knew that it was somewhat ereditary but as my age and addiction progressed and those symptoms started being more prominent I thought that she might be right, anyway as you said time will tell, it's too soon anyway for me to tell how is my brain and body affected. I will go through some brain, body, blood test and rays etc this week to make sure where I should improve.
 

Speed King

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not at all, I would have one question also.

I still have muscle spams beside brain zaps (been clean for 10 days, tonight would be the 11th) are this permanent?

I used to have more frecvent ones in the past while on mega doses and started to have less with tapering, I have read that brain zaps are not dangerous but the muscle spams thing makes me anxious, mainly about it evolving in something worse. My first psychiatrist when I was a teen said that due to prolonged use I may become affected by huntington disease and that was like 5 years ago, so idk if she was trying to scare me as I was younger or it may develop.
I'm glad you quit using the medication. Like Kleinerkiffer said, you will be dealing with side effects for a while. The Magnesium will help out a bit, but your brain has to adjust to not having the medication in your system. I wouldn't focus on side effects or amp yourself about them, but you may have side effects for a while. I would research supplements that may help offset those side effects.

Great thread by the way. I am hoping that you allow us to contribute to this thread.
 

Jabberwocky

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yes of course, you can merge other tramadol threads also when they appear plus add any information. I am glad I quit too, I never felt this good in years. the cravings are still there sometimes for the mood enhancement that tramadol gave me and I still have needle fixation related to my morphine, fent and oxy use but I cope with it pretty well. almost had a relapse about two days ago but talked myself out of it.
 

Lorne???

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Yiur wrong on one big thing: IV admistration doubles(DOUBLES) the Cmax of M1, the active metabolite

So although not advisable, IV is the most efficient roa(I've posted this somewhere, too lazy to do it again)

Other than that decent job
 

Jabberwocky

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might be, but idk why it never worked for me that way. I still got the recreational effects and all but not the same depth of pleasure, but I have to take into calculation in what state was my body in and all kind of psychical/neurological parameters etc. anyway everyone reacts differently to the same subst. but I never felt that doing multiple shots would be worth it or one 10ml shot ( that was my minimum dosage to make the w/d disappear.
 

Jabberwocky

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thanks jekyl! was thinking about doing one about clonazepam (rivotril roche here, klonopin in other parts of the world) and maybe a few other benzos as opioids pretty much have their own Megathreads already and I'm having some free time on hand so i'll try to cover what is not covered heavily and recently.
 

pally pete

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You say Carbamazepine Metabolises the Tramadol quicker but at the same time does it convert more of the Tramadol into DesmeTramadol?
 
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