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  1. Apr 2021
  2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Nimodipine-enhanced opiate analgesia in cancer patients requiring morphine dose escalation: a double-blind, placebo-controlled study
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    1. Drugs_and_Ethics 09 Apr 2021
      Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference being statistically significant (P=0.03).

      Consistent with rat data. This is from 1998. I'm sure there's more evidence by now. It's been a while since i researched this, but I think I've previously seen at least one other study.

      opioid reverse-tolerance supersensitivity
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    pubmed.ncbi.nlm.nih.gov/9696455/
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor
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    1. Drugs_and_Ethics 09 Apr 2021
      These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

      Excellent. This implies that theobromine may help prevent opioid tolerance.

      theobromine opioid tolerance cAMP PDE reverse-tolerance supersensitivity
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    ncbi.nlm.nih.gov/pmc/articles/PMC1572651/