@
Iquitos
Actually, thinking about it, since the half life of cannabidiol (CBD) is long (around 2 to 5 days, ref:
here), once you start taking the CBD oil daily, CBD is going to be in your system at fairly constant levels, no matter what time you take your CBD oil.
Low dose naltrexone (LDN), by contrast, will have left your body within 2 or 3 of taking it. So only for a few hours after taking LDN will you have opioid receptor antagonism from naltrexone.
But of course after those 2 or 3 hours are over, although the opioid receptor antagonism will have ended as the naltrexone leaves your body, you will have higher levels of the opioid met-enkephalin in your body, because the effect of LDN is to create higher levels of met-enkephalin.
So this means you initially have opioid receptor antagonism with LDN, for 2 or 3 hours, then followed by increased opioid receptor agonism (activation) for the rest of the day, due to the higher levels of met-enkephalin in circulation in the body.
If we are talking about the effects of marijuana and tetrahydrocannabinol (THC), then it seems that opioid receptor antagonism from LDN will enhance the effects of marijuana and THC:
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This study found that opioid antagonism from naltrexone enhances the effects of marijuana: naltrexone increases the subjective "high" that users feel from marijuana, and increases the cardiovascular effects of marijuana. Note that marijuana contains both THC and CBD.
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This study also found that ultra low dose naltrexone enhances the pain-relieving effects of THC-like cannabinoids; this study employed a synthetic cannabinoid called
WIN 55,212-2, which like THC, agonizes the CB1 and CB2 cannabinoid receptors.
➤ However, CBD is not THC, so the above studies do not apply to CBD. When it comes to CBD, things seem more complicated:
Unlike THC, CBD has a very low affinity for the CB1 and CB2 cannabinoid receptors. Rather, CBD acts as an
indirect antagonist of the agonist effects of THC-like cannabinoids. In other words, CBD can reduce THC's activation of the cannabinoid receptors. This is according to the Wikipedia article on CBD, which is worth looking at:
Cannabidiol - Wikipedia.
Though Wikipedia also says:
one would assume that CBD would reduce the effects of THC, but in fact CBD may potentiate THC's effects by increasing CB1 receptor density. So it seems that there is no clear indication on whether CBD blocks or potentiates the effects of cannabinoids like THC. It probably does a bit of both.
Likewise, I guess it therefore is not clear whether CBD may block or potentiate the effects of the body's own natural cannabinoids — the
endocannabinoids — on the cannabinoid receptors. These endocannabinoids are involved in appetite, pain-sensation, mood and memory.
It is therefore not very clear how CBD works at the cannabinoid receptors: it seems to have both THC enhancing and THC reducing effects.
So as for any attempt at a theoretical understanding of the interaction between LDN and CBD, it is all about a clear as mud!
I would just stick with your own empirical observation that LDN reduces the effects of CBD, and go with that.
➤ Note that in addition to its effects at the cannabinoid receptors, CBD is also a
5-HT1A serotonin receptor agonist, which apparently relates to CBD's antidepressant, anxiolytic and neuroprotective effects. The Wikipedia article on the
5-HT1A receptor says that the effects of activating this receptor include:
Relieving anxiety and depression
Decreased aggression
Increased sociability
Decreased impulsivity
Facilitation of sex drive and arousal
Inhibition of penile erection
Diminished food intake
Prolongation of REM sleep latency
Improving cognitive functions associated with the prefrontal cortex
Improving symptoms of schizophrenia and Parkinson's
In ME/CFS,
it has been found that there are 5-HT1A receptor abnormalities. Perhaps CBD oil might help rectify these abnormalities?
➤ CBD is in addition a partial agonist of the
5-HT2A serotonin receptor. Activation of this 5-HT2A receptor has potent anti-inflammatory effects: such activation reduces levels of the inflammatory cytokine TNF-alpha (ref:
here).
Activation of the 5-HT2A receptor also causes a release of oxytocin (the love and human bonding hormone), which might explain why Cannabis tends to make people more friendly.
Both the 5-HT1A and 5-HT2A receptors are known to mediate spiritual effects — see this study:
Self-Transcendence as a Measurable Transpersonal Construct
Albert Garcia-Romeu, The Journal of Transpersonal Psychology, 2010, Vol. 42, No. 1
Interestingly, many psychedelic drugs such as LSD and psilocybin activate both 5-HT1A and 5-HT2A, though most of the effects of these psychedelics is mediated by the 5-HT2A receptor.
One important point that should be noted by those trying out CBD oil:
CBD is observed to have a bell-shaped dose-response curve (ref:
here). This means that up to a certain point, increasing your CBD dose will increase its effects; but then after you get to the optimum dosage, further increases in CBD dose will actually result in
reduced effects.