Manage stress and anxiety

The review gives each study's cortisol only at the end of its course, so how soon any fall begins is unknown. The falls it reports are measured against where people started, not against placebo, and one of the nine had no placebo group. The two studies that measured cortisol in saliva disagreed, and one found no change. Extract and dose differ from study to study, from 60 mg to 5 g a day.

The trials recruited adults who already described themselves as highly stressed, so the same fall may not appear in someone whose cortisol starts out ordinary. Four of the nine trials reported mild-to-moderate side effects. Extract and dose differed from trial to trial, so the pooled result describes no one product. The second review's two studies that measured cortisol in saliva rather than blood disagreed, one finding no change at all. In a later 12-week trial of older, overweight adults, stress scores fell about as far on placebo as on ashwagandha, and cortisol was not measured, so the self-rated stress part of this result is less settled than the cortisol part.

Eighty-four separate comparisons across 23 conditions means some significant findings are expected by chance, and most were graded low or very low quality. The missing cannabidiol effect on pain is an absence of evidence inside these trials, not a tested null.

The search closed in April 2018, before several cannabidiol-specific trials were published. The one anxiety signal the review did find came from pharmaceutical THC, in people whose main problem was chronic pain or multiple sclerosis, and was graded very low quality.

Most of the pooled studies took a single snapshot rather than following anyone, so nothing here shows stress moving the surge. The stress measures themselves are a mixed bag, from job strain to burnout, and they do not all point the same way, which is the finding rather than a flaw in it.

The mechanism is shown far more directly in the animal studies than in the human ones, where nobody has followed it over time. And this is about how cells respond rather than how much hormone is present, so a blood cortisol reading says nothing about whether it is happening.

Thirty-four people finished the trial, but the treatment effects were computed on 26 — the ones who had actually reacted to the task at baseline, picked out after the fact. An industry grant funded the study, and the paper says the funder had no hand in the analysis. The other ingredients were phosphatidylserine, alpha-glycerylphosphorylcholine and chamomile, each in a small dose. Why the two effects arrived two hours apart is unexplained. Performance on the task itself never moved.

Thirty-six people enrolled and 34 finished, but the effects were computed on 26, chosen after testing and before unblinding for having reacted to the task at baseline. Four people gave too little saliva and were left out of the cortisol analysis, and the paper does not say how many remained. The drink was not theanine alone: it also carried 25 mg of alpha-glycerylphosphorylcholine, 1 mg of phosphatidylserine and 10 mg of chamomile. Before dosing and at one hour the task did not reliably raise cortisol, so the rise the drink blunted appeared at one session out of three. A grant from a company, Neurobrands, paid for the trial, and the paper says the funder had no input into its design, conduct or interpretation.

Twenty-six of the 34 who finished were analysed, and they were the ones who had reacted to the task at baseline. The drink was not theanine alone: phosphatidylserine, alpha-glycerylphosphorylcholine and chamomile came with it, in small doses. An industry grant funded the trial, and the paper says the funder had no hand in its design or analysis. A brain-wave finding in the same trial turned up only in the more anxious participants and did not track the stress or cortisol results, so it stands unexplained.

The prescription figures are set per kilogram of body weight; the milligram equivalents here use the label's own 75kg reference, and many of the patients in these trials are children. The consumer average has a standard deviation of 40.7mg, nearly as wide as the mean itself.

Single doses in a residential unit, about six people per formulation, so this is not a test of daily use. Cannabidiol did not convert to THC by any route tried here, but only the routes and formulations tried are covered.

Urine, not blood, so these concentrations cannot be set beside the plasma figures on the prescription label. About six people took each formulation, and each took a single dose in a residential unit rather than using the product over time.

Each study sets its own tolerance — a tenth either way here, a stricter band for the drinks — so the percentages describe different tests and should not be pooled. The samples are snapshots too: one online channel in 2016, one US state later, with single-figure counts inside some categories.

Both are dated regional snapshots — products bought online in 2016 and in one US state in 2020 — and neither describes what is on shelves now. The synthetic cannabinoids turned up in vaping products specifically, so nothing here says the same of oils or edibles.

This is a narrative review drawing human and animal work together, not new data. And the arrow could run either way: a stress-disrupted cortisol system might raise autoimmune risk, or years of autoimmune illness might be what disrupts the system. Nothing here separates the two.

The authors describe the effects as small. Everyone measured was young and healthy, at an average age of 20, so this says nothing about older adults or about anyone with a sleep or stress disorder. And these are the same people watched over time rather than an experiment, so something else in their days could be driving both ends.

These were tiny experiments, 13 men in one of them, run over one or two nights. All the participants were young men, so nothing here covers women or older adults. And a night or two of lost sleep is not years of it, so how far the flattening goes over a lifetime is unmeasured.

Eleven trials and 312 people in total, and the authors name the small number of studies as their main limitation. The search closed in August 2013 and nothing comparable has replaced it. No pooled dose is reported, so these results should not be read across to the intakes used in polycystic ovary syndrome supplements.

A report count is not a rate: it says withdrawal made up a large share of a drug's reports, not how many users had it. The drugs with the strongest signals were also the most reported and most talked about, which the authors say may inflate their ratios. Among 19 people who had once stopped fluoxetine, a drug that lingers for weeks, remembered withdrawal was as severe as after venlafaxine.

Twenty-three of the 61 reports were single case reports, and no pooled figure exists for how many people get a prolonged course. The label's drawn-out cases come from voluntary reports with no denominator. NICE puts the usual course at one to two weeks, occasionally months.

This is a gap in what has been measured, not a recorded harm: no trial reported an adrenal problem, because none of them looked for one. Inside their 30-to-112-day windows the trials reported no serious side effects.

The participants skewed middle-aged and older, and most were women. A long list of outcomes was tested at once, which on its own makes some of the positive ones likely to be chance.

A pooled stress effect of nearly six standard deviations would mean almost nobody on placebo scored as low as anyone on ashwagandha, while earlier trials of the herb measured effects of 0.63 to 0.74 standard deviations. The authors themselves note the trials differed widely, and pooling very different trials can produce a size no single trial supports. The dose-response finding is read off the same pooling.

How much ashwagandha eases stress is unsettled. The poolings agree that it helps, but the largest reports an effect several times what single trials measured, and nothing yet explains the gap.

Placebo groups in earlier ashwagandha stress trials barely moved, falling around 5.5%, so a 36% placebo fall may be what hid the difference here rather than a weaker herb. Cortisol was not measured, so this says nothing about the hormone. The fatigue result was one secondary outcome among many measured, which makes a chance finding more likely. The trial was paid for by the extract's maker.

Whether ashwagandha's edge on stress survives a strong placebo response is open. Pooled trials found it beat placebo, but in older, overweight adults the placebo group improved by a third and matched it.

The pooled studies mix one-off experimental stress in healthy volunteers with treating diagnosed anxiety disorders — different questions, answered as one. A large pooled effect resting on trials this small is where the smallest studies dominate, and the authors caution against over-reading it.

Whether cannabidiol eases anxiety is still open. A large pooled effect for cannabidiol alone and scarce benefit across all medicinal cannabinoids, mostly THC trials, answer different questions, so neither settles it.

There was no control group — the comparison is to historical population figures, not a concurrent placebo arm. Blood was drawn once at 30 days, so a delayed signal would not appear. Participants were recruited through twelve cannabidiol companies, and three of four authors declare industry ties.

The prescription label records liver-enzyme rises that a study of people buying cannabidiol for themselves did not find. Doses differ more than tenfold and so do the people, so the split is about who was studied, not the compound.

The three dose figures are second-hand: a 2022 review copied them from a 2005 UK regulator's report, and the report itself is where the counts live. The middle dose came out lower than the lowest, so the rise rests on the 150 mg group alone. The label gives the trend and no number.

The survey reached 18% of those invited, all recalling past attempts, which plausibly inflates every figure, and it did not separate venlafaxine from other antidepressants. The tenfold odds ratio ran from about 3 to 38. The label states the trend without a number. The tapering cohort had no comparison group.

Whether years on venlafaxine make it harder to stop is open. The label and long-term users say yes; the trials that say no lasted only weeks, so they never tested the question.

The percentages were extracted by a later review from the trial's tables; the trial's own summary gives only the direction. Withdrawal was a side outcome of a trial built to compare how well the drugs worked, after eight weeks of use, so it says nothing about longer use. A review of 61 reports found withdrawal most often with venlafaxine but could give no pooled figure.

The trial's taper lengths were chosen by the clinic, not randomised, and ran weeks. The cohort had no group tapering without the strips, and the 608 who rated symptoms daily were a self-selected minority of 3,956 users, most of whom had failed before. The cohort's authors developed the strips.

Whether a slower venlafaxine taper spares withdrawal is unsettled. A cohort that chose slow tapering says yes, a trial with few-week tapers says no, and neither tested the months-long schedule now recommended.