OMr_duckO
2009-01-02, 01:32
Tramadol was developed by the German pharmaceutical company Grunenthal GmbH in the late 1970s and marketed under the trade name Tramal. Now is available in most countries as a prescription pain-reliever and for other off-label uses such as fibromyalgia, opioid dependence, or migraines. In some countries like Thailand or Mexico it is available over-the-counter. Contrary to what most physicians claim about tramadol, who give it out like candy, it is a narcotic. It is an atypical synthetic quasi-narcotic, and has a broad range of effects much like ephedrine.
Pharmacology:
Tramadol itself is a norepinephrine and 5-HT reuptake inhibitor, and a very mild Mu-opioid receptor agonist. After an hour or so, tramadol is metabolized into it’s metabolite M1 (O-desmethyltramadol), which has a 200x greater affinity for mu1, and mu2 opioid receptors. and also has other effects on dopamine and possibly NMDA antagonism. The mu-agonism dis-inhibits dopamine pathways and also causes release of histamine and vasopressin.
Effects:
Some people say that the come-up (pre-metabolism) feels similar to sertraline or the come-up of MDMA. I’d imagine tramadol by itself feels closest to venlaflaxine, an SNRI with some very mild actions on some opioid receptors. The effects after metabolism are often likened to hydrocodone or oxycodone. The comedown isn't very pleasant. You may feel drained and zombie-like, and become agitated easily.
Many people say that the high from this drug feels natural, unlike most other drugs, but people that are more self-aware can discern between a natural and artificial high. When it comes to liking the effects of this drugs it’s hit or miss. You either absolutely love, even more than sex, or you absolutely hate it with a passion. If you’re one of the “Luke-warms” and want to derive pleasure from this drug, you won’t extremely enjoyable, mostly due to it's adverse effects. Effects in list form:
- Calmness. Characterized by a decrease in thought process and anesthesia of emotions, which is a neutral effect because thoughts and emotions can be both negative and positive. This effect is due to the reuptake inhibition of serotonin, the primary action of anti-depressant drugs such as Prozac (fluoxetine), lexapro (citalopram), Zoloft (sertraline), or paxil (paroxetine).
- Increase in physical energy. User may feel an endless supply of energy, and find physical activity more easy or enjoyable. This effect is due to the re-uptake of norepinephrine, the primary action of drugs such as Strattera (Atomoxetine).
- Increase in mental energy. Characterized by increased alertness, motivation, and talkativeness. This is due to the dopaminergic actions caused by dis-inhibition of dopamine pathways through mu-opioid agonism and also maybe through some other mechanism.
- Analgesia. Tramadol has fairly powerful pain-relieving effects, mostly from agonism of mu-opioid receptors, but serotonin-norepinephrine reuptake inhibition and possibly NMDA antagonism and other effects also increase pain-threshold.
- Sedation and respiratory depression. Breathing and heart rate may slow down contributing to the “nod” or “waking dream” effect that opioids are known for. They should be carefully monitored if one suspects overdose. Opioid antagonists should always be kept handy if ever one isn’t careful and ingests too much of an opioid.
- Difficulty urination. Caused by increase in anti-diurhetic hormone vasopressin. It will make you retain water more, and urination may be extremely difficult. I’ve often stood over the toilet for long periods of time before I can get a trickle of urine to come out. Though fortunately tramadol makes you more patient than you normally would be. This adverse effect can be countered with caffeine, which blocks vasopressin. A kappa-opioid receptor agonist like pentazocine or ethanol would also work in theory, though tramadol dose should be reduced to prevent excessive respiratory depression and other undesirable or dangerous effects from too much opioids.
- Itching. Caused by histamine release. Can be easily countered with administration of an anti-histamine. An OTC medication called Claritin (loratadine) is the cleanest anti-histamine to my knowledge with the least side-effects.
- Nausea and/or vomiting. Nausea (and hyperthermia) typically occurs when too much dopamine is released in a certain part of the brain, but may also be caused by stomach disturbances from ingesting the tramadol orally. Can be remedied with OTC anti-emetics such as pepto bismol or Dramamine.
- Seizures. Tramadol can cause seizures especially if taken in excess of 400mg's. Seizures can occur even in doses as low as 50mg’s in people with naturally low seizure thresholds, so epileptics should definitely stay away from this drug. Intravenous use may increase probability of seizures.
- Sexual dysfunction - Serotonin and norepinephrine have negative effects on sex drive, even though they are both neccesary for acheiving an orgasm. 5-HT by decreasing desire and NE by decreasing blood flow to genitals. Pure opioids just cause anorgasmia and basically makes it all difficult, though I dont know much of the mechanism behind this.
Some other adverse effects may include agitation, headaches, anxiety, weakness, heartburn, sweating, tremor, and vertigo.
Overall, the effects are mostly well-balanced, with stimulation of both sympathetic and parasympathetic nervous system to give a calm, relaxed, yet energized sense of well-being.
However, Tramadol alone is probably the worst drug to get addicted to. Generally, the withdrawals overall are considered to be worst than that of heroin. So it should not be taken more than once every 3 days to avoid addiction and tolerance.
Combinations:
For a single-use of tramadol I recommend taking it with a benzodiazepine like clonazepam, diazepam, or alprazolam. They will even out the noradrenergic actions which cause physical anxiety and aggression, and heighten seizure threshold. Cannabis is also a very good drug to combine, as with many drugs, but too much can overpower it and exacerbate adverse effects. OTC medication diphenhydramine (brand unisom, sominex, benadryl) can counter adverse effects of tramadol including itching, nausea, vertigo, and can potentiate calming effect and sedation. Tramadol is also available in conjunction with paracetamol/acetaminophen or aspirin.
Tramadol should NOT be combined with other drugs that are known to cause seizures like Bupropion (wellbutrin, zyban). There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g. SSRI’s) or with use of a light box, since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism. Tramadol may also weaken the effects of psychedelic drugs such as tryptamines (ie. LSD, psylocybe mushrooms,etc.), phenethylamines (mescaline, 2C-X’s, etc.), and ecstacy (MD(x)A). Cocaine should also be especially avoided. Rapper Ol’ dirty bastard died from mixing cocaine with tramadol, though exact cause of death is not known whether itwas serotonin syndrome, overdose, or both.
Dosing and methods of administration:
For starters (if you are opiate naive, recommend starting with 50mg's and then redosing another 50mg's an hour later. It's best this way because the bioavailability increases with repeated dosing, up to 100%. You can re-dose as much as you think you can handle, but it generally takes up to an hour for the opiate agonism to start working go slow, and do not exceed 450mg's. The best method of administration would be rectal if you have the pills. To administer them via this route, crush them up as finely as possible, dissolve in some warm water, draw up into a rectal or oral syringe, turkey baster, or a douche bag, and inject it into your rectum. Rectal is best because the bioavailability is 77% first administration, as opposed to 68-72% when taken orally, and the quickness of onset and intensity of effects is between that of oral and intranasal ROA . If you have high purity human or lab grade tramadol powder than intramuscular or intravenous injection would be the best way for a recreational experience. You won't get a significant opiate rush, but the effects and metabolism will come on much faster.
.
Pharmacology:
Tramadol itself is a norepinephrine and 5-HT reuptake inhibitor, and a very mild Mu-opioid receptor agonist. After an hour or so, tramadol is metabolized into it’s metabolite M1 (O-desmethyltramadol), which has a 200x greater affinity for mu1, and mu2 opioid receptors. and also has other effects on dopamine and possibly NMDA antagonism. The mu-agonism dis-inhibits dopamine pathways and also causes release of histamine and vasopressin.
Effects:
Some people say that the come-up (pre-metabolism) feels similar to sertraline or the come-up of MDMA. I’d imagine tramadol by itself feels closest to venlaflaxine, an SNRI with some very mild actions on some opioid receptors. The effects after metabolism are often likened to hydrocodone or oxycodone. The comedown isn't very pleasant. You may feel drained and zombie-like, and become agitated easily.
Many people say that the high from this drug feels natural, unlike most other drugs, but people that are more self-aware can discern between a natural and artificial high. When it comes to liking the effects of this drugs it’s hit or miss. You either absolutely love, even more than sex, or you absolutely hate it with a passion. If you’re one of the “Luke-warms” and want to derive pleasure from this drug, you won’t extremely enjoyable, mostly due to it's adverse effects. Effects in list form:
- Calmness. Characterized by a decrease in thought process and anesthesia of emotions, which is a neutral effect because thoughts and emotions can be both negative and positive. This effect is due to the reuptake inhibition of serotonin, the primary action of anti-depressant drugs such as Prozac (fluoxetine), lexapro (citalopram), Zoloft (sertraline), or paxil (paroxetine).
- Increase in physical energy. User may feel an endless supply of energy, and find physical activity more easy or enjoyable. This effect is due to the re-uptake of norepinephrine, the primary action of drugs such as Strattera (Atomoxetine).
- Increase in mental energy. Characterized by increased alertness, motivation, and talkativeness. This is due to the dopaminergic actions caused by dis-inhibition of dopamine pathways through mu-opioid agonism and also maybe through some other mechanism.
- Analgesia. Tramadol has fairly powerful pain-relieving effects, mostly from agonism of mu-opioid receptors, but serotonin-norepinephrine reuptake inhibition and possibly NMDA antagonism and other effects also increase pain-threshold.
- Sedation and respiratory depression. Breathing and heart rate may slow down contributing to the “nod” or “waking dream” effect that opioids are known for. They should be carefully monitored if one suspects overdose. Opioid antagonists should always be kept handy if ever one isn’t careful and ingests too much of an opioid.
- Difficulty urination. Caused by increase in anti-diurhetic hormone vasopressin. It will make you retain water more, and urination may be extremely difficult. I’ve often stood over the toilet for long periods of time before I can get a trickle of urine to come out. Though fortunately tramadol makes you more patient than you normally would be. This adverse effect can be countered with caffeine, which blocks vasopressin. A kappa-opioid receptor agonist like pentazocine or ethanol would also work in theory, though tramadol dose should be reduced to prevent excessive respiratory depression and other undesirable or dangerous effects from too much opioids.
- Itching. Caused by histamine release. Can be easily countered with administration of an anti-histamine. An OTC medication called Claritin (loratadine) is the cleanest anti-histamine to my knowledge with the least side-effects.
- Nausea and/or vomiting. Nausea (and hyperthermia) typically occurs when too much dopamine is released in a certain part of the brain, but may also be caused by stomach disturbances from ingesting the tramadol orally. Can be remedied with OTC anti-emetics such as pepto bismol or Dramamine.
- Seizures. Tramadol can cause seizures especially if taken in excess of 400mg's. Seizures can occur even in doses as low as 50mg’s in people with naturally low seizure thresholds, so epileptics should definitely stay away from this drug. Intravenous use may increase probability of seizures.
- Sexual dysfunction - Serotonin and norepinephrine have negative effects on sex drive, even though they are both neccesary for acheiving an orgasm. 5-HT by decreasing desire and NE by decreasing blood flow to genitals. Pure opioids just cause anorgasmia and basically makes it all difficult, though I dont know much of the mechanism behind this.
Some other adverse effects may include agitation, headaches, anxiety, weakness, heartburn, sweating, tremor, and vertigo.
Overall, the effects are mostly well-balanced, with stimulation of both sympathetic and parasympathetic nervous system to give a calm, relaxed, yet energized sense of well-being.
However, Tramadol alone is probably the worst drug to get addicted to. Generally, the withdrawals overall are considered to be worst than that of heroin. So it should not be taken more than once every 3 days to avoid addiction and tolerance.
Combinations:
For a single-use of tramadol I recommend taking it with a benzodiazepine like clonazepam, diazepam, or alprazolam. They will even out the noradrenergic actions which cause physical anxiety and aggression, and heighten seizure threshold. Cannabis is also a very good drug to combine, as with many drugs, but too much can overpower it and exacerbate adverse effects. OTC medication diphenhydramine (brand unisom, sominex, benadryl) can counter adverse effects of tramadol including itching, nausea, vertigo, and can potentiate calming effect and sedation. Tramadol is also available in conjunction with paracetamol/acetaminophen or aspirin.
Tramadol should NOT be combined with other drugs that are known to cause seizures like Bupropion (wellbutrin, zyban). There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g. SSRI’s) or with use of a light box, since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism. Tramadol may also weaken the effects of psychedelic drugs such as tryptamines (ie. LSD, psylocybe mushrooms,etc.), phenethylamines (mescaline, 2C-X’s, etc.), and ecstacy (MD(x)A). Cocaine should also be especially avoided. Rapper Ol’ dirty bastard died from mixing cocaine with tramadol, though exact cause of death is not known whether itwas serotonin syndrome, overdose, or both.
Dosing and methods of administration:
For starters (if you are opiate naive, recommend starting with 50mg's and then redosing another 50mg's an hour later. It's best this way because the bioavailability increases with repeated dosing, up to 100%. You can re-dose as much as you think you can handle, but it generally takes up to an hour for the opiate agonism to start working go slow, and do not exceed 450mg's. The best method of administration would be rectal if you have the pills. To administer them via this route, crush them up as finely as possible, dissolve in some warm water, draw up into a rectal or oral syringe, turkey baster, or a douche bag, and inject it into your rectum. Rectal is best because the bioavailability is 77% first administration, as opposed to 68-72% when taken orally, and the quickness of onset and intensity of effects is between that of oral and intranasal ROA . If you have high purity human or lab grade tramadol powder than intramuscular or intravenous injection would be the best way for a recreational experience. You won't get a significant opiate rush, but the effects and metabolism will come on much faster.
.