Jump to content
The Corroboree
Alchemica

Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity

Recommended Posts

A clinical trial is currently underway/actively recruiting, using L-tetrahydropalmatine as an adjunctive treatment for schizophrenia. I have covered it in 'Improving the treatment of schizophrenia - a summary' but think it deserves a thread of its own. It may be a safer, more tolerable alternative to clozapine [possibly requiring higher doses than those in the clinical trial if used as a single antipsychotic].

Does anyone have experience with acute or longer term administration of corydalis extract/THP they wish to share? I'm particularly interested in hearing from anyone who may have used it in psychotic illness and if they found any benefit.

Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity

Schizophrenia is a devastating and complex illness, with multiple symptom and behavioral manifestations. Antipsychotic medications are the mainstay of treatment; however, many patients only partially respond to treatment. Development of new treatment has not progressed rapidly, in part, because the underlying etiopathophysiology of the illness is not well understood. To date, all pharmacological treatments approved for use in schizophrenia involve primary modulation of the dopamine system. Many agents without dopamine action have failed to demonstrate efficacy. There is growing evidence that schizophrenia may be, in part, due to an inflammatory process and pharmacological treatment approaches that decrease inflammation have shown promise. Thus, treatments that may have anti-inflammatory properties (e.g., TNF-alpha inhibition), but also possess dopamine modulation may prove to be beneficial. This novel medication, l-tetrahydropalmatine (l-THP), has robust anti-inflammatory properties, particularly TNF-alpha and ICAM inhibition; has antiprotozoal activity; and possesses an antipsychotic-like pharmacological profile of D1, D2 and D3 receptor antagonism. The high affinity of l-THP for D1 versus D2 receptors distinguishes it from first generation antipsychotics and its D1 to D2 ratio resembles that of the superior antipsychotic, clozapine. Also, an almost identical compound, l-stepholindine (l-SPD), demonstrates robust antipsychotic activity in humans (both positive and negative symptoms) and is currently used clinically in China. l-THP has been used for over 40 years clinically in China, has a good safety profile to date, and represents a novel and exciting mechanism for schizophrenia treatment. Initial safety data from our phase I study of l-THP (20 healthy controls) shows excellent tolerability and lack of any substantial side effects. L-THP has been tested in outpatient drug abuse trials for 4 weeks with good safety data, (Hu et al 2006, Yang et al 2003). Yang et al (2003) randomized this medication in over 120 participants for 4 weeks with 4 week observation without any notable side effects.

We will test this compound (30 mg BID) as an adjunct treatment in a randomized, double-blind, 4-week trial, in which we will assess treatment efficacy, changes in peripheral cytokine concentrations, and, secondarily, antiprotozoal effects, (antibody titers to Toxoplasma gondii), an infection that is known to occur at higher rates in schizophrenia than healthy controls and may be related in part to the illness.


Condition Intervention

Schizophrenia

Drug: L-tetrahydropalmatine (30mg)
Drug: Sugar pill

L-tetrahydropalmatine - a D1/D2 antagonist (with multiple relevant pharmacological targets, including affinity for the sigma-1 receptor [18b]), may offer some benefit but research into its use in schizophrenia is lacking.

220px-Tetrahydropalmatine.png

"L-tetrahydropalmatine (l-THP), has robust anti-inflammatory properties, particularly TNF-alpha and ICAM inhibition; has antiprotozoal activity; and possesses an antipsychotic-like pharmacological profile of D1, D2 and D3 receptor antagonism. The high affinity of l-THP for D1 versus D2 receptors distinguishes it from first generation antipsychotics and its D1 to D2 ratio resembles that of the superior antipsychotic, clozapine" [link]

- D1 receptor antagonist with a Ki of 94 ± 9 - 124 nM and an IC50 value of 166 nM
- D2 receptor antagonist with a Ki of 388 nM and an IC50 value of 1.47 μM

- inhibits voltage gated calcium channels in a manner similar to verapamil
- Shows weak inhibitory activity against the dopamine D3 receptor with IC50 of 3.25 μM
- In addition to the antagonism of postsynaptic dopamine receptors, inhibition of presynaptic autoreceptors by THP leads to increased dopamine release, which is probably attributed to lower affinity towards D2 receptors.
- Potently inhibits 5-HT1A with IC50 of 374 nM and Ki of 340 nM
- Interacts with a number of other receptor types, including α-1 adrenergic receptors, at which it functions as an antagonist, and γ-aminobutyric acid receptors, at which it facilitates γ-aminobutyric acid binding through positive allosteric effects.

- Attenuates the rewarding effects of drugs of abuse, including stimulants and opioids. It may be an effective anti-addiction therapy.

Edited by Alchemica
  • Like 3

Share this post


Link to post
Share on other sites

Some would argue shizo is a condition of the mind and not a treatable disorder. Like its a trained behavioural condition causing symptom falling into shizo catorgory rather than an genetic/ hereditry/ or drug induced physical/chemical disorder.?

Ive never met a skit whos treatment fixed the orders that proclaimed the prognosis.

There help is in there head they just cant utilize it.

Personally, i enjoy the occasional voices in the head.

  • Like 1

Share this post


Link to post
Share on other sites

I read somewhere that it can be sometimes be hard diagnosed via urine test, the article said they urinated tryptemines of the diamond mine kind

if i can relocate the article i will add it here, but just off memory for now

bear in mind some drs throw mental diagnoses round like confetti at a wedding though

not all of them.

found it: - no its not, this one blows the one i had in mind out of the water

-always a lot of info out there to shit filter i guess

http://www.ncbi.nlm.nih.gov/pubmed/1070024

perhaps it was used abused as a source to then twist into some misinfo at some point

Edited by ☽Ţ ҉ĥϋηϠ₡яღ☯ॐ€ðяئॐ♡Pϟiℓℴϟℴ
  • Like 1

Share this post


Link to post
Share on other sites

Some would argue shizo is a condition of the mind and not a treatable disorder. Like its a trained behavioural condition causing symptom falling into shizo catorgory rather than an genetic/ hereditry/ or drug induced physical/chemical disorder.?

Ive never met a skit whos treatment fixed the orders that proclaimed the prognosis.

Over longer periods, prognosis varies. Overall, 1/3 of patients achieve significant and lasting improvement; 1/3 improve some but have intermittent relapses and residual disability; and 1/3 are severely and permanently incapacitated [1]

There seem to be differing views and I struggle to find a happy medium...

1. Early intervention with pharmacological and social interventions is critical and medication should be continued. Under the biomedical model, schizophrenia is a severe, highly disabling and lifelong condition requiring lifelong medication:

“Clinicians should be encouraged to treat early to reduce the duration of untreated psychosis, particularly delusions. The emergence of psychosis is a very important time to intervene, and even subtle symptoms could herald future deterioration. The goal is to treat effectively, aiming for full remission of psychotic symptoms. In doing so, clinicians should offer their patients a full armamentarium of interventions to improve their long-term outcome and functioning. This includes combining medication with cognitive-behavioral or other therapies to minimize stress and optimize psychosocial outcome; and using job coaching, cognitive remediation, or other strategies to achieve and retain a full functional recovery.”

2. Pharmacological interventions may not be needed:

“Diagnostic classification and its often stigmatizing effects do not do justice to the uncertainty of prognosis nor the potential inefficiency and risks of routine pharmacological approaches. Prescription of neuroleptics should be cautious and postponed, especially given the availability of sound alternatives with more modest, short-term roles for medication…

Eradicating [symptoms] pharmacologically, even if patients understandably request this, is not always a realistic treatment goal. Limitations in the existing evidence base for neuroleptic medication for voices have been highlighted, and it has been argued that there is not enough robust evidence to support the routine administration of such medication for voice-hearers (who are diagnosed with psychosis)”

3. Holistic and spiritual approaches may be effective:

“…some psychiatric states are opportunities for spiritual growth rather than intrinsically destructive psychopathologies”

There help is in there head they just cant utilize it.

I'm on the 'superior' antipsychotic clozapine [which has some really nasty side-effects], another new expensive one and huge doses of antidepressant and I can't say it's done much for the most distressing symptoms, the 'voices'. One of my goals at the moment is to come off the clozapine, or decrease it further.

While I'm neurotically searching for the panacea that will rid me of these 'voices' and tackle some social/emotional/cognitive deficits, realistically I'm probably going to need to accept that medication isn't going to be THE answer.

I've got plenty of past intrapsychic conflicts that hopefully will gradually 'dissolve' and leave the 'voices' with nothing to constantly torment me over. Maybe one day I'll also get to "enjoy the occasional voices in the head."

The most helpful things haven't been in 'my head', rather 'our heads'. Socially reconnecting, tackling anxiety and developing social skills with a support worker, getting out into the community garden, planning to get back to study and a bit of intensive psychological therapy have been important aspects in getting somewhat better.

Then there are the highly effective and more 'heart-centered' things like getting a dog and maintenance of friendships.

Exercise has also been a very grounding activity and definitely gives me a break from my head.

bear in mind some drs throw mental diagnoses round like confetti at a wedding though

not all of them.

Very true. I've collected quite a few of them over the years. Probably even inadvertently wanted them, just to have a reason to explain why I was so unhappy with myself and why I felt so different.

That said, I haven't been kind to myself emotionally/spiritually over the years and have complicated things with various substance abuse issues and suicide attempts so it gets messy...

Despite investment in research and treatment, the outcomes of patients diagnosed with the most severe psychiatric disorders have not improved since the Victorian period. Where are the flaws in our understanding? Mental health treatment needs a radical overhaul to bring it into the 21st century – but what needs to change?

… get up to speed with what’s fact and what’s fiction about schizophrenia with Professor and Clinical Psychologist Richard Bentall as he debunk the common myths in this free online course: Nine Myths About Schizophrenia.

The course above is quite interesting so far (but the videos seem to take forever to load) - I'd recommend it to anyone who might be interested :)

Back on the use of L-tetrahydropalmatine:

¤ L-THP may have interactions with other medications [ii]

:excl: Tetrahydropalmatine should be considered for herb-drug interactions in clinical therapy until relevant clinical studies are available. Be cautious if you decide to use it alongside other medications

Edited by Alchemica
  • Like 1

Share this post


Link to post
Share on other sites

i like number 3 a lot , one of my exes was a schizophrenic but i couldn't tell at all , she was very magickal/spiritual and absolutely fantastic human , ..."if only partners were always faithful tho..." :rolleyes:

regardless though , her magick actually worked!

and still does.

They are definitely awesome in their own way especially when calm and happy.

I know 2 here that seem more like they are oppressed than schitzophrenic but still pummel away the zyprexa and "die" when they sleep but are hard working people and have awesome personalities if given a chance

i know of one other whi is particularly nasty though and not much else about them other than having been to school with them.

misdiagnoses of psychiatric disorders is a little too common for my liking where i live

after some personal experience and "lurning curve" i can say this first hand but have not yet got round to how to sue them for it

also know a three personality "spirit hopping vessel" and it is absolutely fascinating to see them at their best

and getting along fine with "eachother" - absolute fantastic addition to the human race beneficial for many already where they live

talking to each of them can be a challenge but makes sense if you can keep up like in say for example

a verbal version of a multiple person internet chatroom

*sends bliss wishes and positive energy*

Edited by ☽Ţ ҉ĥϋηϠ₡яღ☯ॐ€ðяئॐ♡Pϟiℓℴϟℴ
  • Like 1

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now

×