13 Matching Annotations
  1. Mar 2019
    1. We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice.

      H1 antihistamines enhance the opioid high in humans. Hospitals sometimes administer antihistamines in combination with opioids. It's not hard to find people online who are using this combination recreationally.

  2. Jan 2019
    1. Table 1. Analgesic potency of nalorphine compared with morphine for postoperative pain*

      2 mg appears most effective. download PDF here.

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    1. . Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects

      I would not expect doses this small to impact the opioid receptors.

    1. Treatment effects were more pronounced at discharge

      Symptoms in the treatment group continually improved, whereas symptoms in the placebo group plateaued. Thus, I'm interested in seeing a longer treatment period. Projecting from symptom scores, elimination of symptoms would occur in about 10 days.

  3. Nov 2018
    1. 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). The dose of morphine was reduced from 313±52 to 174±33 mg/day (P<0.001) in the nimodipine group, and from 254±26 to 218±19 mg/day (not significant) in the placebo group.

      Nimodipine reduced morphine dose in already tolerant patients.

    1. The full text describes how ultra-low-dose naloxone and naltrexone enhance opioids at very slim dose margins. A mere two fold difference on naltrexone dose can determine efficacy: 2 micrograms is effective whereas 4 is not. What's more, this optimal dose changes with sex, mouse strain, opioid agonist used, etc.; this making precise dosing challenging. The mechanism suggested is that filamin A has two binding sites, where only 1 has the desired effect.

    1. We measure the binding affinity of NLX or naltrexone to FLNA in cell membranes as 4 picomolar, i.e. approximately 200-fold higher than their binding affinity for MOR

      This sentence appears to indicate equal potency between the two drugs.

    2. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs.

      So, naloxone has a 200 times higher potency at Filamin A compared to opioid receptors, but I need clarification on whether naltrexone achieves similar potency.

  4. Aug 2018
    1. Prazosin had no analgesic effect alone but dose-dependently potentiated morphine analgesia in morphine-naive mice. Another alpha(1)-adrenoceptor antagonist, corynanthine, had similar effects. Prazosin also increased the analgesic potency of the morphine test dose in morphine-tolerant mice. Naloxone-precipitated vertical jumping was not affected, but weight loss was reduced by prazosin. Acutely administered clonidine potentiated morphine analgesia and alleviated opioid withdrawal signs, as expected. We conclude that in addition to the already established involvement of alpha(2)-adrenoceptors in opioid actions, also alpha(1)-adrenoceptors have significant modulatory role in opioid analgesia and withdrawal.

      This is interesting but not exactly surprising, given that both are depressants. What is surprising, however, is the contrast between this and the fact that stimulants also enhance morphine analgesia.

      Potentiation of Opioid Analgesia by Psychostimulant Drugs: A Review00084-0/fulltext)

  5. Dec 2017
    1. If the South Bronx were a state, it would have the second highest rate of drug overdose in the country after West Virginia.

      Wow! Very sad and disturbing.

  6. Nov 2017
    1. His doctor cut off his supply and urged Hale to enter a detox program. That didn’t work. Hale, still in agonizing pain and now suffering from intense withdrawal symptoms, returned to his doctor and pleaded to get back on his opioid regime. The doctor refused.
  7. Oct 2017
    1. Trump blindsides advisers with promised opioid plan Officials are scrambling to produce an emergency declaration by next week.