Obscure and Unknown: Analgesic Psychotria Alkaloids

*WARNING* The substances (the pure substances, not the plant material, which has been used medicinally for time immemorial) mentioned in this post have little to no record of human use, and thus the effects they have on humans are either poorly understood or entirely unknown. With these substances specifically, there simply is too little information to deem them safe, the toxicity and full receptor profile is simply too poorly understood for now, and similar compounds like Eseroline have aberrant toxicity. This seems like an easy experiment to do but PLEASE exercise an abundance of caution. Much of what this information is simply hypotheses based on animal trials or very small human sample sizes. Very little information exists about their acute or long-term toxicity. Under no circumstances should any of these substances be ingested by a human outside of a clinical setting where psychological and physiological effects can be closely monitored and extremely precise doses can be prepared and TITRATED. DO NOT seek any of these out if you do not have access to those resources.

Hello, today we will be looking at some potentially psychoactive alkaloids that can be found in plants of the genus Psychotria. Psychotria is a genus of plants found worldwide across the tropics, in the family Rubiaceae, the same family which contains the coffee plant. They typically grow as woody shrubs or small trees in jungle understories. Several species are well known for their entheogenic usage. There is evidence to suggest that the active chemicals in a few species may perhaps function as NMDA antagonist-dissociatives. If this is the case, they would be some of the only naturally occurring NMDA-antagonist dissociatives known. Some other NMDA antagonists are known in nature (Polygala tenuifolia, linalool, Rhynchophylline, Magnesium)29, 30, 31, 32 though they have not yet been observed to have strong hallucinatory dissociative effects. One species in particular that contains these interesting alkaloids is P. colorata, which has a long record of medicinal use by indigenous people in Brazil.

Now, before I get into the rest of the article I want to clarify that it is in no way confirmed that these alkaloids will have hallucinogenic dissociative effects in humans. There is evidence suggesting that may be the case, but so far, it is not enough to draw meaningful conclusions. Nevertheless, I think it's an interesting possibility and that is why I am writing about it. I will lay out that evidence in this piece, and you can decide for yourself. I personally think that at the very least, further formal and more detailed research is warranted for these interesting compounds!

Psychotria colorata

If you're clever, you may see this name and think "Psychoactive alkaloid from Psychotria? Hmmm I know one!" Yes, this genus is perhaps best known for the species Psychotria viridis, which contains DMT and is a standard ingredient in traditional preparations of Ayahuasca (There are also several other more obscure species of Psychotria that contain DMT). P. viridis is not the only species in that genus to contain bioactive alkaloids however- One species has in fact, has been used in traditional medicine for its interesting analgesic properties: Psychotria colorata1, Other species have been recently conjectured to have likely analgesic properties too, namely P. lyciiflora2 , P. oleoides2, P. forsteriana7, P. beccarioides8 and P. umbellata3.

Several alkaloids have been isolated from these species of Psychotria to which the analgesic effects are attributed- these are, namely, Hodgkinsine, Psychotridine, and Psychollatine. What is most interesting about these compounds is their seemingly mixed activity analgesia- the main ways in which anesthesia is achieved is through opioid receptor agonism (primarily the μ-opioid receptor) or NMDA antagonism, the method by which dissociative hallucinogens work. These Pscyhotria alkaloids have uniquely demonstrated specific functional similarities to both in animals (detailed more in my assessment of each compound). Hodgkinsine has in fact been confirmed to be a weak μ-opioid agonist, though this stands to be confirmed in the other compounds. Meanwhile, whether they truly have affinity for the NMDA receptor, and if they do, whether that would elicit effects similar to dissociative hallucinogens in humans, is still completely unknown. The data that suggest this method of action are based on analogous behavioral effects in animals, and a full receptor affinity study has not yet been performed. Also worth noting is that the different alkaloids seem to have different mechanisms of action.

Reading this you may also have your memory jogged about another jungle plant that serves as an analgesic with mixed receptor activity, though it primarily has opioid activity- Kratom, by means of the compounds 7-Hydroxymitragynine, Mitragynine, and Mitragynine pseudoindoxyl. Could these Psychotria species fill a similar role to Kratom as it comes under increasing legal scrutiny and prohibition? There simply isn't enough information about these Psychotria species and their active alkaloids to say so for now, and to say so would risk subjecting a rare plant used as medicine by indigenous peoples to overharvesting, if it is not cultivated responsibly and sustainably. But the possibility is there, pending further study to definitively determine the pharmacology of these alkaloids and their exact effects in humans. 

Here is a handy chart for which species contain which alkaloids:

Species	Analgesic Alkaloids
Psychotria colorata	Hodgkinsine5, Psychotridine6
Psychotria lyciiflora	Hodgkinsine2
Psychotria oleoides	Hodgkinsine2, Psychotridine2
Psychotria forsteriana	Psychotridine7
Psychotria beccaroides	Psychotridine8
Psychotria umbellata	Psychollatine3

First let's look at the species involved here in more detail, then we can look into the different alkaloids.

Psychotria colorata

Psychotria colorata

Psychotria colorata is by far the best known species of Pschotria that contains analgesic alkaloids. It is found in the jungles of Northeastern Brazil. It has traditionally been used by the Ka'apor people for various purposes such as fishing bait9. Among the peasantry of the Caboclo (mixed indigenous and European ancestry), it is renowned for its analgesic properties, used primarily to treat earache and abdominal pain10. 

The traditional preparation of P. colorata involved wrapping flowers in banana leaves and gently warming them over hot coals before before mixing them with milk, filtering them, and applying the them topically to affected areas. Other formulations are made by boiling the roots and berries11. 

The analgesic effects of P. colorata are attributed to a constellation of alkaloids working in tandem- Best studied are Hodgkinsine and Psychotridine, which have possible NMDA antagonist activity. These two compounds are surveyed in detail further on in the writing.

After sharing this post online, someone on reddit from Brazil had actually stated that they had had experience using Psychotria colorata. They described their experience as such:

"Very relaxed feeling, between light benzo dose with a little codeine, I use a lot when I want to give benzos a break, off course with other plants but alone is very soothing, calming and sometimes of the dose is high or very concentrated makes me itch a little, because of this I always thought it’s have some opioid activity"

Some other analgesic P. colorata alkaloids

There are also a handful of other alkaloids found in P. colorata that have possible analegsic effects, namely (+)-Chimanthonine, (-)-Chimanthonine, and Meso-chimanthonine. These compounds show varying degrees of affinity for the μ-opioid receptor (with some being stronger than Hodgkinsine) and doubtful possible activity on the NMDA receptor, so they will not be discussed further4. P. colorata also contains some other alkaloids of unknown or absent bioactivity, namely Quadrigemine C, (-)-Calycanthine, and Isocalycanthine11. Based on structural patterns with expanding on the pyrrolidinoindoline monomer, I would hypothesize that Quadrigemine may also have analgesic effects. All of these alkaloids come together to give us the pain relief that indigenous people have observed in P. colorata for so long.

Pscyhotria Lyciiflora

Preserved specimen of Psychotria lyciiflora

Psychotria lyciiflora (aka Margaritopsis lyciiflora) is an obscure species of Psychotria that is only known from New Caledonia, an island to the east of Australia. P. lyciiflora also contains the alkaloid Hodgkinsine2. It additionally  shares the alkaloid meso-chimanthonine with P. colorata, and also contains a unique analogue called Nb-desmethyl-meso-chimonanthine of unknown effects. It is interesting to note that it shares these fairly complex alkaloids with a species that is literally on the other side of the earth-whether this is convergent evolution or whether this is a divergent phenotype that simply has not been discovered in other species yet is still entirely unknown. P. lyciifloria has no known history of medical use by people. 

Psychotria Oleoides

Preserved specimen of Psychotria oleoides

Psychotria oleioides (aka Margaritopsis oleioides) is also found exclusively on the island of New Caledonia. It is probably closely related to P. lyciiflora. P. oleoides also contains the ever so popular Hodgkinsine, though it additionally contains a whole set of different alkaloids, namely Psychotridine, Quadrigemine, Quadrigemine I, Isopscyhotridine, Oleoidine, and Caledonine2. While the bioactivity of most of these is either negligible or has not yet been determined, Psychotridine is known to be an analgesic with a mechanism of action similar to Hodgkinsine13. Psychotridine, along with  Isopscyhotridine and Quadrigemine, are known to inhibit platelet aggregation (they act as a type of blood thinner)7. Similar to P. lyciiflora, P. oleoides has no history of human or medicinal use. 

Pscyhotria forsteriana

Psychotria forsteriana

Psychotria forsteriana (Though it is sometimes placed in the genus Eumachus or Uragoga) is another species of Psyhotria from Oceania, this one being found on the islands of Vanuatu, directly northeast of New Caledonia. It contains the alkaloids Psychotridine, Quadrigemine A, Quadrigemine B, and Isopsychotridine7. It also has no recorded history of human or medicinal usage.

Psychotria beccaroides

Psychotria beccaroides, reported to live in the jungle understory of New Guinea, is the most obscure Psychotria species listed here. In fact, I could find so little information on it that I am doubtful whether or not it is even a valid taxon. Nonetheless, a single report states that it is known to contain Psychotridine8. A writeup on Ayahuasca also stated that it contains compounds similar to Emetine (the active alkaloid in ipecac, a formulation used to induce vomiting), which would make P. beccaroides potentially toxic or at the very least nauseating to consume13. There seems to exist no other information on this species.

Pscyhotria umbellata

Psychotria umbellata

Psychotria umbellata (Better known as Psychotria brachypoda) is the most unique of the analgesic Psychotria species by way of its unique alkaloid called Psychollatine (formerly known as Umbellatine). Its range is given as Brazil14,  though another species with this given name is found in Western Africa15. It is likely that this is an unresolved taxonomic revision. It seems that It is the only species in the genus Psychotria to produce the alkaloid Psychollatine, which has been clearly demonstrated as having analgesic properties, with strong indicators towards μ-opioid agonism and NMDA antagonism3. An ethanol extract from the dried leaves was determined to contain the highest concentration of the analgesic alkaloid3. It is not known to contain any other alkaloids. This species also has no history of human or medicinal use.

Now with that out of the way, lets look at some of the compounds responsible for the interesting analgesic effects that have been observed. 

Hodgkinsine

Hodgkinsine is the most studied and best known analgesic Pscyhotria alkaloid, having been primarily observed in Pscyhotria colorata. It was later discovered to also be present in Psychotria lyciiflora and Psychotria oleoides2, and may exist in other species. It was first discovered in the plant Hodgkinsonia frutescens (another member of the coffee family, Rubacieae) in 194916. It is named for this plant, the only plant known to contain it outside of the genus Psychotria.

If you've been reading my other articles, the first thing you may notice about this molecule relative to other psychoactive molecules is, well, it's very big. This molecule is a trimer, meaning it is composed of three identical subunits bonded together. The subunits in question are pyrrolidinoindolines, which bear a passing resemblance to the tryptamine molecule. 

The analgesic properties of Hodgkinsine were first studied in depth in 1995 by Elisabetsky et al., under the context of studying indigenous medical use of Psychotria colorata11. An aqueous extract of the leaves was prepared, as Hodgkinsine had not yet been identified as the active compound. A series of tests with mice confirmed its analgesic properties, along with determining they were partially inhibited at naloxone11. This suggested that its analgesic properties were a result of μ-opioid receptor agonism. Another study from around the same time further determined and quantified its opioid effects17. This would be a recurring observation as experiments continued.

Over time, Hodgkinsine was identified as an alkaloid in P. colorata18, and was later determined to be the main active alkaloid responsible for its analgesic properties19. Several elegant syntheses were discovered and published, allowing for it to be easily studied in a lab11, 20. 

The first of these studies followed the lead of the original analgesic studies done with the extract. The exact behaviors studied were writhing (a pain response to either acetic acid or formalin), the tail flick (the mouse flicks its tail in response to increasing directed on it), and the thermal plate test (timing the animal's reaction to a hot plate of increasing temperature). These are standard tests used to determine the effectiveness of analgesics, and with this cluster of tests, specifically opioid analgesia4, 11, 17, 19, 20. A Capsaicin pain response was done too, which is a specific test for analgesics that act as NMDA antagonists4, 19, 20. The theory behind these different tests is that opioid analgesics help with alleviating actual mechanical pain, while NMDA antagonists are useful in suppressing neurogenic pain (as capsaicin induces a sort of "illusory" pain without causing any actual physical harm). Indeed ketamine is at times prescribed for neuropathic pain. There was a dose-dependent inhibition of a pain response observed for all of these tests, supporting a hypothesis of Hodgkinsine acting as an analgesic on the μ-opioid and NMDA receptors4, 11, 17, 19, 20. Nonetheless, an NMDA receptor affinity study is warranted for a final determination on this.

One study by Verotta et al. looked into the μ-opioid receptor affinity for Hodgkinsine and the Chimanthonine alkaloids from the same plant4. It has a significantly lower affinity for the μ-opioid receptor than morphine, suggesting it is a weak opioid4. This is curious, as it had demonstrable opioid-like properties both in the mouse response to thermal stress, and in its ability to be inhibited (partially) by naloxone. Perhaps some other mechanism is at work here. It should also be noted that at the doses tested, there were no noteworthy aberrant behavioral effects that may be observed with hallucinatory dissociatives.

What kind of doses does Hodgkinsine have active pain relief effects? And at what doses may other effects present? Responses to thermal pain equivalent to that of an effective dose of morphine were seen at doses of 5-20 mg/kg via intraperitoneal injection19. In a 70 kg human, these would be doses of 350-1400 mg. Meanwhile, a capsaicin pain relief response equivalent to an effective dose of MK-801 was observed at 2.5 mg/kg, 175 mg in a 70 kg human19. It is unknown what the doses would be via other routes of administration or what the pharmacokinetics of the substance are that may effect dosing via other means such as oral. It would appear that the effects that mimic that of NMDA antagonists present first, with stronger opioid effects occurring in higher doses. This raises interesting questions per human experiences with this substance- would you feel dissociative analgesia before opioid analgesia? Has this been reported at all? Indeed some form of analgesia is felt in humans from consuming Psychotria colorata, but no qualitative descriptions of this currently exist. The nature of it however, led to opioid properties being initially investigated, so that suggests that it feels similar to them. But perhaps this has something to do with the pharmacokinetics and the route of administration used- this all warrants further investigation in humans to truly determine the answers! It is also worth nothing that these are low end threshold analgesic effects- more interesting effects may present at higher doses than what is given here, but it is all still entirely unknown what it may do in humans.

Another study by Kodanko et al. looked into several enantiomers and analogues of Hodgkinsine20. While most of the enantiomers were inactive, one unnamed analogue with additional methyl groups on the pyrrolidines demonstrated a higher potency, active at 2.5 mg/kg20.

A possibly more potent analogue of Hodgkinsine (I may have gotten the stereochemistry wrong... Another diagram is in [20] in the citations, please let me know if this needs corrected!)

So what's the verdict with Hodgkinsine? Well it's definitely an analgesic, indigenous people have known this fora long time. It's a weak μ-opioid agonist, but appears to present clear opioid properties in response to thermal pain, and it is inhibited by Naloxone. So it is safe to say that Hodgkinsine is an opioid of some sort- its affinity for the other opioid receptors is as of yet unknown. As for NMDA antagonist dissociative activity? Well the capsaicin test is supported by demonstrations that MK-80121 and Ketamine22 can help suppress capsaicin induced pain responses. So the fact that a similar effect was seen with Hodgkinsine seems to support NMDA antagonist activity. However, some studies show opioid agonists can also have this effect, possibly rendering that test worthless in distinguishing the mechanism of an analgesic23. So in my opinion, Hodgkinsine as an NMDA antagonist is still dubious. This could be easily proven or disproven with a simple receptor affinity study. But time will tell. It would appear that if there were dissociative effects, they would present at a lower dose than the opioid effects- such dose-effect gradients with differing receptor activity can be seen in Kratom. Furthermore, all of these studies were only performed with rodents- the analgesic properties of pure Hodgkinsine in humans, in terms of subjective qualia, dosage, pharmacokinetics, etc. has not been formally studied in detail. We don't know until we try! There remains so much to be learned about this interesting compound and I hope these questions can be answered someday. 

Psychotridine

Psychotridine is a large molecule- a pentamer composed of 5 pyrrolidinoindolines (the same subunit as Hodgkinsine) joined together. In other words, Hodgkinsine is 3 pyrrolidinoindolines, Psychotridine is 5 of them. Many of the functional analgesic properties of Hodgkinsine are conserved in this extension (and indeed opioid activity can be seen in the dimer (2) form of the pyrrolidinoindolines, the Chimanthonines). Thus it would follow that a tetramer (4) of pyrrolidinoindolines would probably also conserve analgesic effects. The tetramer of  pyrrolidinoindoline is known as Quadrigemine, and its isomers can be found in H. frutescens, P. colorata, P. oleoides, and P. forsteriana24. No studies have yet been performed on the bioactivity or analgesic effects of Quadrigemine, though I personally hypothesize that it may have analgesic effects just based on the pattern of activity in pyrrolidinoindoline polymers. 

Pscyhotridine is seen across several species of Pscyhotria, namely P. colorata, P. oleoides, P. forsteriana, and P. beccaroides6, 7, 25. In P. colorata, the known analgesic effects were at first mostly attributed to Hodgkinsine, though it is now known that Psychotridine plays a part too. While the other species have not been bioassayed in humans for their analgesic effects, it is likely that their Psychotridine content would lend them that effect.

There exists one study surveying the analgesic effects of Psychotridine, which was interestingly focused primarily on its possible activity as an NMDA antagonist6. The results of this study were very interesting- firstly there was a clear analgesic effect in the tail-flick test, and a capsaicin test saw analgesia comparable to that of known dissociative MK-8016. Interestingly, co-administration of Naloxone at the same time had no effect on the drug, suggesting that it has no opioid activity. That would leave NMDA antagonism as the main mechanism by which Pscyhotridine suppresses pain. One other test that clearly indicated NMDA antagonist activity was membrane binding test, in which it was found that Psychotridine inhibited binding of MK-801. This means that Psychotridine is likely binding to the same receptor (the NMDA receptor) more competitively, blocking MK-801 from binding. All of this goes to strongly suggest that Psychotridine is an NMDA antagonist. All that's needed to confirm it is a receptor affinity study. Whether it acts as an NMDA antagonist in a way that would induce hallucinatory dissociative effects is still unknown however. 

The dosages of Psychotridine found analgesia comparable to an active dose of morphine at 10 mg/kg via subctaneous injection (700 mg in a 70 kg human), and effects comparable to an analgesic dose of MK-801 at 2.5 mg/kg via the same route (175 mg in a 70 kg human)6. As before, these are low end analgesic and medical effects, not necessarily an "interesting" dose, and as before these effects may be highly dependent on pharmacokinetics in humans, which are as of yet unknown.

Quadrigemine A

With the evidence strongly suggesting that Psychotridine is an NMDA antagonist, we get a more complete portrait of the cocktail of alkaloids that give P. colorata its well known analgesic effects- Hodgkinsine acting as a weak opioid agonist and possible NMDA antagonist, Psychotridine acting as a likely NMDA antagonist, Chimonanthines acting as slightly stronger opioid agonists, and still unknown activity from Quadrigemine, which based on structural patterns, is probably also analgesic in some way. A pattern I hypothesize is that increasing the number of subunits in the pyrrolidinoindoline polymer increases NMDA antagonist activity while decreasing opioid activity, and vice versa, seeing as Pyschotridine, with 5 pyrrolidinoindolines, shows the weakest opioid activity but the most likely NMDA activity, while the Chimonanthines have the strongest opioid activity of the Psychotria alkaloids4. It would be interesting to see the polymer expanded further (if that is a possible), to a hexamer or heptamer, to see what effects continue to arise. Further testing is required to refine this hypothesis however.

Psychollatine

Psychollatine

Psychollatine, formerly known as Umbellatine12 is found only in one species of Psychotria- Psychotria umbellata (formerly, and still sometimes known as Psychotria brachypoda12). The nomenclature is confusing and there are multiple conflicting sources that seem valid, I am not 100% sure that these all refer to the same thing, but I am assuming they are. There also appears to be  species called Psychotria umbellata that lives in Africa and likely is not the analgesic one found in Brazil that I am referring to here. Perhaps that needs revision.

Psychollatine is unique in only containing a single pyrrolidinoindoline, along with another heterocyclic monoterpene ring structure, attached to a glucose. 

The first study on Psychollatine was within the context of using a preparation of the plant material of Psychotria umbellata as an analgesic26. The tail-flick test showed clear dose-dependent analgesia, inhibited by naloxone, suggesting a degree of opioid activity26. Another test that demonstrated similarity with opioids was a drop in body temperature24.

The compound was later isolated, synthesized, and studied on its own. It is not known if P. umbellata has a cocktail of active alkaloids like P. colorata, but it appears not. Testing of the purified compound led to corroboration of the opioid-like effects along with observed similarity to NMDA antagonists via the capsaicin test3. The authors note that Psychollatine " apparently combines opioid activation and NMDA antagonism properties. The exact mode of interaction of umbellatine with these receptor types are therefore worth investigating"3

It's NMDA antagonist properties are further investigated in another study in which it was determined to prevent glutamate induced seizures, clear NMDA antagonist activity27. More interesting however, was its demonstrated properties in reducing MK-801 induced stimulation and reducing amphetamine induced mortality27. These observations indicate that it functions as a dopamine antagonist, and in reducing the effects of stimulant drugs, it would be considered a sedative depressant most similar to antipsychotics. 

So now we see Opioid, NMDA antagonist, Anti-dopaminergic effects in this single drug. What else can it do? Another study looked into its activity on serotonergic systems and GABA systems, other pathways by which many psychoactive substances work (Psychedelics and stimulants mostly, and depressants, respectively)28. Through a variety of tests, several interesting observations about Psychollatine were made- It had anxiolytic properties similar to Diazepam, though it was not affected by a GABA inhibitor (which would inhibit Diazepam) so it probably doesn't share a mechanism of action, thus it is likely not GABAergic like benzodiazepines and alcohol28. A forced swimming test, often used to determine candidates for antidepressants, showed similar effects between Psychollatine and Fluoxetine (Prozac)28. Lastly, a series of tests determined that it had amnesiac affects on memory. The memory and antidepressant effects suggest some form of serotonergic activity, the authors suggest serotonin antagonism, specifically on the 5HT2A/C receptors28. They also suggest the amnesiac effects could be from anticholinergic activity, or as a secondary effect of the suggested NMDA antagonism28. 

So these studies have gone out and determined that Pyschollatine has the possibility of acting on almost every neurotransmitter pathway that psychoactive substances can act on, making it an extremely nonselective substance- perhaps not suited for medical uses because of an extremely high possibility of unpredictable side effects. Just what do we see? Very likely is opioid activity, NMDA antagonist activiy, and anti-dopaminergic effects. Also likely is some sort of activity on the 5HT2A/C receptors, and conjectured anticholinergic activity. This is a substance that would probably make you feel a lot of ways at the same time- if it is anti-dopaminergic and anti-serotonergic it would likely not even be a pleasant experience, it may in fact be fairly dysphoric. But it would certainly help relieve pain. It should be noted that all of this receptor activity is just conjectured from behavioral responses in mice- a more complete picture would strongly benefit from a receptor affinity assay. 

Dosages? Anesthetic effects equivalent to morphine were seen at doses of 300 mg/kg (21000 mg or 21 g in an average human- a very high dose of any drug!), while capsaicin responses equivalent to MK-801 were seen at 200 mg/kg (14000 mg, also very high)3. This would make it the least potent of the Psychotria alkaloids by a significant margin. As before, these are low end analgesic and medical effects, not necessarily an "interesting" dose, and as before these effects may be highly dependent on pharmacokinetics in humans, which are as of yet unknown.

Conclusion

Wow this ended up being much longer than i expected. I guess my final points are these: analgesic properties have clearly been observed in some species of Psychotria, in the case of Psychotria colorata, this has been observed for a very long time. This is attributed to pyrrolidinoindoline, often in the form of polymers. The dimer, the Chimonanthines, seem to have strongest opioid activity. The best studied however is the trimer, Hodgkinsine, considered to be the primary active alkaloid, which shows low opioid affinity but marked opioid and NMDA-antagonist behavioral effects. The tetramer Quadrigemine is still poorly known. The pentamer Psychotridine shows probable NMDA-antagonist effects only and no discernible opioid effects. Lastly, Psychollatine, not a pyrrolidinoindoline polymer, shows opioid and NMDA antagonist behavioral effects. Psychollatine also had the distinction of having behavioral effects related to other receptors studied- in which probable anti-dopaminergic, anti-serotonergic, and conjectued anticholinergic activity were observed. It is entirely possible that the other alkaloids would have this extreme nonselectivity for receptors, they just haven't been tested for them yet. But also behavioral responses can only really give us hints at receptor activity and elucidate paths for further investigation- all of these substances need further study such as receptor affinity assays to better determine their activity and the effects they may have in humans.

Okay, that was a lot of jargon, again in English: The most interesting possibility here is that Psychotria alkaloids may present mixed opioid-dissociative effects at higher doses. This would be seen in Hodgkinsine and Psychollatine (with added anxiolytic sedative effects), and Psychotridine may display only dissociative effects. It is also entirely possible that they just may not behave that way in humans at all or yield an interesting experience- drugs are fickle. The answer to this simply will not be known until someone goes and finds it out (see warning at top though). At the very least, even if you can't *trip* on Psychotria alkaloids lol, they still may prove useful analgesics for unique circumstances, perhaps filling a role similar to Kratom, though further study is needed to see if it could meet those purposes. 

One last note is that, while i tried to be as comprehensive as possible with listing analgesic species and their alkaloids, one source gave a whole, longer list of Psychotria species to which analgesic properties were attributed26. I looked into some of these and could find only scant information, but the chart is included here, the literature they mention is cited in citation [32] onwards in the sources and further reading section if you want to look into it more yourself. It's worth nothing that this article uses the disputed name Psychotria brachypoda, and it may be possible that the species names listed in it are also disputed and may be known under other names.

Table of other possibly analgesic Psychotria species from Leal & Elisabetsky 2008. Happy searching! Who knows what other fascinating alkaloids may be hiding out there!

Sources and Further Reading:
1- Elisabetsky E, Amador TA, Albuquerque RR, Nunes DS, Carvalho Ado C (1995) Analgesic activity of Psychotria colorata (Willd. ex R. & S.) Muell. Arg. alkaloids. Journal of Ethnopharmacology 48(2):77-83
2- Jannic V, Guéritte F, Laprévote O, Serani L, Martin MT, Sévenet T, Potier P (1999) Pyrrolidinoindoline alkaloids from Psychotria oleoides and Psychotria lyciiflora. Journal of Natural Products 62(6):838-843
3- Both FL, Kerber VA, Henriques AT, Elisabetsky E (2002) Analgesic Properties of Umbellatine from Psychotria umbellata. Pharmaceutical Biology 40(5):336-341
4-Verotta L, Orsini F, Sbacchi M, Scheildler MA, Amador TA, Elisabetsky E (2002) Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids. Bioorganic & Medicinal Chemistry 10(7):2133-2142
5- Verotta L, Pilati T, Tatò M, Elisabetsky E, Amador TA, Nunes DS (1998) Pyrrolidinoindoline Alkaloids from Psychotria colorata. Journal of Natural Products 61(3):392-396
6- Amador TA, Verotta L, Nunes DS, Elisabetsky E (2001) Involvement of NMDA receptors in the analgesic properties of psychotridine. Phytomedicine 8(3):202-206.

7- Beretz A, Roth-Georger A, Corre G, Kuballa B, Anton R, Cazenave JP (1985) Polyindolinic alkaloids from Psychotria forsteriana. Potent inhibitors of the aggregation of human platelets. Planta Med. (4):300-303.

8-  Hart N, Johns S, Lamberton J, Summons R (1974) Psychotridine, a C55H62N10 Alkaloid From Psychotria beccarioides (Rubiaceae). Australian Journal of Chemistry 27:639-646

9- Balée W (1994) Footprints of the Forest: Ka’apor Ethnobotany—the Historical Ecology of Plant Utilization by an Amazonian People. New York: Columbia University Press.

10- Elisabetsky E, Castilhos Z (1990). Plants Used as Analgesics by Amazonian Caboclos as a Basis for Selecting Plants for Investigation. Pharmaceutical Biology 28:309-320

11- Elisabetsky E, Amador TA, Albuquerque RR, Nunes DS, Carvalho Ado C (1995) Analgesic activity of Psychotria colorata (Willd. ex R. & S.) Muell. Arg. alkaloids. J Ethnopharmacol 48(2):77-83

12- Porto D, Henriques A, Fett-Neto Arthur (2009). Bioactive Alkaloids from South American Psychotria and Related Species. The Open Bioactive Compounds Journal. 2:29-36

13- https://erowid.org/library/books_online/ayahuasca_apa/aya_sec3_part1_psychotria.shtml

14- Paranhos JT, Fragoso V, Henriques AT, Ferreira AG, Fett-Neto AG (2005) Regeneration of Psychotria umbellata and production of the analgesic indole alkaloid umbellatine. Tree Physiol. 25(2):251-255

15- https://www.gbif.org/species/2898997

16- Anet EFLJ, Hughes GK, Ritchie E (1961) Hodgkinsine, the Alkaloid of Hodgkinsonia frutescens F. Muell. Australian Journal of Chemistry 14:173-174

17- Amador TA, Elisabetsky E, Souza DO (1996) Effects of Psychotria colorata alkaloids in brain opioid system. Neurochem Res. 21(1):97-102

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