Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): L-tetrahydropalmatine (30mg); Sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): Active comparator; Placebo
Intervention MeSH terms: Tetrahydropalmatine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment