Yesterday SWIM woke up and took five 37.5 mg tramadol pills. after this SWIM was given a chance to purchase some doses from a sheet with a picture of the Rolling Stones on it.
SWIM ate one tab and noticed that after an hour and a half nothing was happening so SWIM decided to take another tab. after about another hour the LSD began to work but it was much different.
the level of confusion and the whole mind trip part of acid was pretty much gone. the tramadol forced SWIM into a fixed mood it seemed. However, SWIM still noticed
visual effects: trails, enhanced color, etc.
All in all it was a disappointment and a waste of acid because the main features of the trip were gone, in fact this was very naive of SWIM to do knowing that Tramadol acts in a similar way of SSRI's which block LSD
Please be extremely careful with this combination in the future. Co-administering Tramadol with any psychedelic is the equivalent of walking on very, very thin ice. My chimp speaks from a most unfortunately jarring personal experience; after waiting a full 12 hours between the ingestion of 125mg Tramadol, the chimp ingested 7mg 5-MeO-MIPT (Moxy). After about a 30min onset, the chimp was absolutely bed-ridden for the next 3.5 hours - which literally felt like multiple nights, no exageration - coping with fevers, overly-intense visual hallucinations of a markedly malignant nature, uncontrollable cognitive & emotional dissonance, and horrendously unpleasant tactile sensations. Not to mention, his bed was utterly wet and sticky with sweat and tears. Despite a strong familiarity & history with such compounds, this was the chimp's first and last introduction to serotonin syndrome - and he considers himself quite lucky to have come out unscathed (he feels unscathed, at least). While Moxy and LSD are admittedly different at the structural level, their activities at serotonergic proteins are quite comparable.
Higher doses of LSD combined with Tramadol will almost certainly generate the conditions for serotonin syndrome to occur. Almost any other opiate would be okay, but specifically Tramadol combined with psychedelics is quite dangerous. This is because, in addition to its lovely µ-opioid activity, Tramadol has SSRI/SNRI activity, and enhances the amount of serotonin available in synapses to bind to receptors - it is a serotonergic agonist. LSD is also a serotonin agonist. These similar activities would be anticipated to cross-potentiate, and generate a dangerous condition termed serotonin syndrome. I'm glad this combination was recreationally disspointing - exploring higher doses of both combined will undoubtedly prove less fruitful, and more dangerous.
This is a significantly misunderstood dynamic. It's not that SSRIs block the psychedelic activity of these compounds, though it may seem that way. Rather, it's that the summed activity of both compounds that changes the nature of the experience altogether. While LSD alone potently induces generalized cognitive/sensory synesthesia, the introduction of SSRI activity will alter the activity of LSD at serotonergic proteins - thereby potentially diminishing the psychedelic return, but not necessarily reducing the compound's effects. The LSD is still there, but it's activity has been modified by the presence of an SSRI. In other words, just because one doesn't feel a normal acid trip from ingesting LSD with an SSRI doesn't mean that the SSRI abolished the receptor activity of the psychedelic. Rather, it means that this activity of the compound has been 're-routed' - and this can be potentially quite dangerous at higher doses, and depending on the nature of the psychedelic.
wow thanks a lot Gradient, that makes sense. The thought of serotonin syndrome crossed SWIM's mind at one point during the trip but SWIM dismissed it as over worrying. SWIM at one point felt an overwhelming sensation in which my heart raced and this heat rushed over SWIM's body, the same feeling SWIM experienced screwing around with DXM, Cannabis, & amphetamines.
SWIM is now curious how does the combo of MDMA and LSD not cause this as well?
Well, this is all debatable - and many will likely disagree with me with cellular studies to back up their arguments, which is entirely valid. However, I feel as though there's something more complicated than advocates of the SSRI-reducing-LSD efficacy argument concern themselves with. While most SSRIs will indeed likely attenuate the psychedelic component of LSD by inhibition of 5-HT2A receptors, it has agonistic actions at other serotonergic receptors, as well as receptor-systems that modulate the activity of serotonergic receptors, that might be important to consider.
However, while more commonly used SSRIs may actually be quite safe to combine, Tramadol has additional atypical effects outside of selective serotonin re-uptake inhibition that may act along with psychedelics to promote serotonin syndrome.
The primary support for the combination to be considered safe is the fact that LSD has activity at a slew of serotonergic receptor-proteins, including the autoreceptors 5-HT1A/B. The function of autoreceptors is to be sensitive to fluctuating levels of a given neurotransmitter, and modulate the amount of neurotransmitter available to bind to receptors in synapses by increasing or diminishing the re-uptake of the given molecule out of synapses, and back into synaptic bodies - thereby preventing over-stimulation of a given neurotransmitter. Activation of these autoreceptors by LSD is suggested to be sufficient to clear up dangerous levels of accumulated serotonin from synapses - preventing the potential for serotonin syndrome.
Tramadol isn't a typical SSRI or Opiate - it's an atypical amalgamation, assembling the activities of both types of compounds into a single administration; I'm convinced that this combination creates consequences that wouldn't be anticipated from the co-administration of LSD with a more typical SSRI or opioid. Here's one thread of thought that's kept me convinced, and it doesn't pertain to serotonin syndrome specifically, but the effects would be indistinguishable. LSD acts at alpha-adrenergic receptor cites as an agonist, while Tramadol inhibits the activity of norepinephrine transmitter proteins - responsible for the trafficking of norepinephrine molecules out of the synapse, and back into vesicles (preventing activation of norepinephrine receptors). At higher doses of both, this might be anticipated as dangerous to healthy function of the circulatory system by allowing an over-abundance of norepinephrine to activate alpha-adrenergic receptor sites (involved in smooth muscle function, heart regulation, circulation).
When it comes to serotonin receptors, different molecules will behave differently at various sub-receptors; not all SSRIs will do the exact same thing to the exact same receptor-proteins. Accordingly, among other things, the aggregate output of Tramadol is to inhibit the re-uptake of serotonin from synapses. Here's a quote from the attached article discussing this dynamic:
Quote:
Tramadol decreases the binding of frontocortical ß-adrenoceptors, 5-HT2A receptors, and alpha2-adrenoreceptors, whereas it increases the binding of alpha1-adrenoceptors and dopamine D2/D3 receptors.
Tramadol and it's metabolites also bind to µ-opioid receptors, involved widely in nociception and euphoric components of commonly used opiates such as morphine & heroin. The attached article also articulates the absence of any absolute understanding of the dynamics characterizing identified relationships between opioid and serotonergic systems. Here's a relevant statement:
Quote:
Interaction of the serotonergic and opioid systems has been documented in animal models concerning pain modulation. The exact mechanism by which 5-HT is involved in the effects of opioids has been questioned. It's well known that 5-HT pays a multifaceted role in the regulation of nociceptive transmission. Our results are consistent with the involvement of the 5-HT system in opioid-analgesia, probably via 5-HT1A receptors preventing the reduction of 5-HT release in terminal areas...Our results are consistent with the hypothesis that the serotonin system is closely involved in tramadol antinociception...The involvement of 5-HT1 receptors in this anti-neuropathic pain remains unclear.
While the interaction of typical SSRI compounds may be more simple to reduce down to receptor-substrate interactions, the fact that Tramadol acts at opioid receptor sites leads me to believe that there may be a consequential downstream enhancement of serotonin release that distinguishes the action of Tramadol from other SSRIs. Accordingly, while SSRIs may indeed prove to be safe to combine with psychedelics, Tramadol may be the odd-one-out due to its ancillary action at opioid sites.
25-06-2009, 20:38
). While Moxy and LSD are admittedly different at the structural level, their activities at serotonergic proteins are quite comparable.
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