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@ARTICLE{Rohleder:1047477,
      author       = {Rohleder, Cathrin and Pahlisch, Franziska and Graf, Rudolf
                      and Endepols, Heike and Leweke, F. Markus},
      title        = {{D}ifferent pharmaceutical preparations of
                      Δ9‐tetrahydrocannabinol differentially affect its
                      behavioral effects in rats},
      journal      = {Addiction biology},
      volume       = {25},
      number       = {3},
      issn         = {1355-6215},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {FZJ-2025-04328},
      pages        = {e12745},
      year         = {2020},
      abstract     = {Based on the contribution of the endocannabinoid system to
                      the pathophysiology of schizophrenia, the primary
                      pro-psychotic ingredient of Cannabis sativa,
                      Δ-9-tetrahydrocannabinol (Δ-9-THC), is used in preclinical
                      as well as clinical research to mimic schizophrenia-like
                      symptoms. While it is common to administer lipid-based
                      formulations of Δ-9-THC in human studies orally,
                      intraperitoneal injections of water-based solutions are used
                      in animal models. Because of the poor water solubility of
                      Δ-9-THC, solubilizers such as ethanol and/or emulsifiers
                      are needed for these preparations. In order to test whether
                      a lipid-based solvent would be superior over a water-based
                      vehicle in rats, we compared the effects on locomotor
                      activity and prepulse inhibition (PPI) of the acoustic
                      startle reaction, as well as pharmacokinetic data obtained
                      from rats' serum and brain tissue samples. Up to 50 mg/kg
                      Δ-9-THC in the lipid-based formulation was not able to
                      induce any behavioral alterations, while already 5 mg/kg of
                      the water-based Δ-9-THC preparation significantly reduced
                      locomotor activity. This also induced a small but
                      significant PPI reduction, which was prepulse intensity
                      dependent. Interestingly, the reflexive motor response to
                      the startle stimulus was not affected by the water-based
                      Δ-9-THC solution. Analysis of serum and brain Δ-9-THC
                      levels by high-performance liquid chromatography/mass
                      spectrometry revealed that although the final concentration
                      reached in the brain was comparable for both pharmaceutical
                      preparations, the water-based formulation achieved a faster
                      kinetic. We, therefore, conclude that the slope of the
                      Δ-9-THC concentration-time curve and the resulting
                      cannabinoid receptor type 1 activation per time unit are
                      responsible for the induction of behavioral alterations.},
      cin          = {INM-5},
      ddc          = {540},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1111/adb.12745},
      url          = {https://juser.fz-juelich.de/record/1047477},
}