Level 4 lockdown arrived and while greeted with much jubilation, also sadly demonstrated just how much homo sapiens residing in South Africa have not changed at their core.

Title: High-Dose Vitamin B Risky for Diabetics With Kidney Disease
Category: Health News
Created: 4/27/2010 4:10:00 PM
Last Editorial Review: 4/28/2010 12:00:00 AM

Title: Lower-Dose Radioiodine Effective Against Thyroid Cancer
Category: Health News
Created: 5/2/2012 6:06:00 PM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: Low-Dose 'Pill' Linked to Pain During Orgasm, Study Finds
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Higher Doses of Antidepressants Linked to Suicidal Behavior in Young Patients: Study
Category: Health News
Created: 4/28/2014 4:36:00 PM
Last Editorial Review: 4/29/2014 12:00:00 AM

Title: Wider Use of Naloxone Could Cut Deaths From Drug Overdoses: CDC
Category: Health News
Created: 4/24/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM

Title: Low-Dose Aspirin Tied to Better Cancer Survival in Study
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM

Title: Low-Dose Aspirin May Lower Risk for Common Breast Cancer by 20 Percent
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM

Title: Fentanyl Now Drives Drug Overdose Deaths in U.S.
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: One High Dose of Radiation May Be Enough for Early Prostate Cancer
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Overdose Attempts Skyrocket Among Teens, Young Adults: Study
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: One Dose of HPV Vaccine May Protect Against Cervical Cancer
Category: Health News
Created: 2/10/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM

This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10⁴ PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS_MA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10⁶ PFU UV-inactivated MERS_MA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.

IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.

ABSTRACT

Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum. Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.

Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 10⁸ CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 10⁹ CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 10⁸-CFU standard dose (n = 50) or a ≥2 x 10⁹-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time period, resulting in metabolic effects superior to those of amylin. Because of the prolonged receptor activation, different dosing intervals and, hence, less frequent receptor activation might change the efficacy of DACRA treatment in terms of weight loss and food preference. In this study, we compared daily dosing to dosing every other day with the aim of understanding the optimal balance between efficacy and tolerability. Obese and lean male Sprague-Dawley rats were treated with the DACRA KBP-088, applying two different dosing intervals (1.5 nmol/kg once daily and 3 nmol/kg every other day) to assess the effect on body weight, food intake, glucose tolerance, and food preference when given the choice between chow (13% fat) and a high-fat diet (60% fat). Treatment with KBP-088 induced significant weight loss, reduction in adiposity, improvement in glucose control, and altered food preference toward food that is less calorie-dense. KBP-088 dosed every other day (3 nmol/kg) was superior to KBP-088 once daily (1.5 nmol/kg) in terms of weight loss and improvement of food preference. The beneficial effects were evident in both lean and obese rats. Hence, dosing KBP-088 every other day positively affects overall efficacy on metabolic parameters regardless of the lean/obese state, suggesting that less-frequent dosing with KBP-088 could be feasible.

Inhaled corticosteroid/long-acting β₂-agonist combination therapy is a recommended treatment option for patients with chronic obstructive pulmonary disease (COPD) and increased exacerbation risk, particularly those with elevated blood eosinophil levels. SOPHOS (NCT02727660) evaluated the efficacy and safety of two doses of budesonide/formoterol fumarate dihydrate metered dose inhaler (BFF MDI) versus formoterol fumarate dihydrate (FF) MDI, each delivered using co-suspension delivery technology, in patients with moderate-to-very severe COPD and a history of exacerbations.

In this phase 3, randomised, double-blind, parallel-group, 12–52-week, variable length study, patients received twice-daily BFF MDI 320/10 µg or 160/10 µg, or FF MDI 10 µg. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV₁) at week 12. Secondary and other endpoints included assessments of moderate/severe COPD exacerbations and safety.

The primary analysis (modified intent-to-treat) population included 1843 patients (BFF MDI 320/10 µg, n=619; BFF MDI 160/10 µg, n=617; and FF MDI, n=607). BFF MDI 320/10 µg and 160/10 µg improved morning pre-dose trough FEV₁ at week 12 versus FF MDI (least squares mean differences 34 mL [p=0.0081] and 32 mL [p=0.0134], respectively), increased time to first exacerbation (hazard ratios 0.827 [p=0.0441] and 0.803 [p=0.0198], respectively) and reduced exacerbation rate (rate ratios 0.67 [p=0.0001] and 0.71 [p=0.0010], respectively). Lung function and exacerbation benefits were driven by patients with blood eosinophil counts ≥150 cells·mm^–3. The incidence of adverse events was similar, and pneumonia rates were low (≤2.4%) across treatments.

SOPHOS demonstrated the efficacy and tolerability of BFF MDI 320/10 µg and 160/10 µg in patients with moderate-to-very severe COPD at increased risk of exacerbations.

In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group.

Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials.

We investigated dose-fractionated polymyxin B (PB) on acute kidney injury (AKI). PB at 12 mg of drug/kg of body weight per day (once, twice, and thrice daily) was administered in rats over 72 h. The thrice-daily group demonstrated the highest KIM-1 increase (P = 0.018) versus that of the controls (P = 0.99) and histopathological damage (P = 0.013). A three-compartment model best described the data (bias, 0.129 mg/liter; imprecision, 0.729 mg²/liter²; R², 0.652,). Area under the concentration-time curve at 24 h (AUC₂₄) values were similar (P = 0.87). The thrice-daily dosing scheme resulted in the most PB-associated AKI in a rat model.

Enterococcus faecium strains are commonly resistant to vancomycin and β-lactams. In addition, E. faecium often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of dosing regimens using daptomycin (DAP) (8, 10, 12, and 14 mg/kg of body weight/day) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm), namely, strains S447 and HOU503, in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions, whereas S447 lacks mutations associated with the LiaFSR pathway. MIC results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT, and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) were used with titanium and polyurethane coupons to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF enhanced DAP activity, allowing DAP 8 and 10 plus ERT or RIF to produce bactericidal activity against both strains at 168 h. While DAP 8 and 10 plus CPT improved killing, they did not reach bactericidal reduction against S447. Combination of AMP, CPT, ERT, or RIF resulted in enhanced and bactericidal activity for DAP against HOU503 at 168 h. Our data provide further support for the use of combinations of DAP with AMP, ERT, CPT, and RIF in infections caused by biofilm producing VREfm. Further research involving DAP combinations against biofilm-producing enterococci is warranted.

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8–11.1] months. In HER2-mutant non–small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1–14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors.

Background:

Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case–control study.

Does being exposed to more virus particles mean you’ll develop more severe illness? Data suggests the relationship between infection and severity may be complex

Bill Gates has been big on vaccines since before the start of the coronavirus pandemic, but in a new blog posting, the Microsoft co-founder and billionaire philanthropist says the only way to end the pandemic for good is to offer a vaccine to almost all of the planet's 7 billion inhabitants. That's big. "We've never delivered something to every corner of the world before," Gates notes. It's especially big considering that a vaccine hasn't yet been approved for widespread use, and that it may take as long as a year to 18 months to win approval and start distribution. Some… Read More

The expectation is the U.S. won’t return to normal until there’s an effective vaccine against COVID-19  — and almost everyone in the country has been vaccinated.

Perfect for the armchair traveller

For continued prevention of recurrent VTE

Calling the rise in overdose deaths from heroin and other prescription pain-killers an “urgent public health crisis,” Attorney General Eric Holder vowed Monday that the Justice Department would combat the epidemic through a mix of enforcement and treatment efforts. As an added step, the Attorney General is also encouraging law enforcement agencies to train and equip their personnel with the life-saving, overdose-reversal drug known as naloxone.

Lupin Pharmaceuticals Inc. (LUPIN, 500257) on Monday announced positive top-line results from its pivotal Phase 3 clinical trial to assess the efficacy and safety of single-dose Solosec or secnidazole 2g oral granules in 147 female patients with trichomoniasis.

Moderna announces it has partnered with Lonza with the aim of producing one billion doses annually.

Pfizer and BioNTech have begun dosing participants in a U.S. clinical trial of their COVID-19 vaccine candidates. The dose-escalation stage of the trial will enroll up to 360 subjects, initially out of sites in New York and Maryland.

Global debt has reached a level not seen since 1970. The current environment of low interest rates and subpar growth performance has triggered a debate about benefits and costs associated with debt. This debate has mainly focused on advanced economies. However, emerging market and developing economies (EMDEs) also face record-low borrowing costs and many have…

Who says newsletters are old school? We pick the best of each day's TreeHugger and add a little je ne sais quoi

Once a week, your cuteness prescription will always be automatically refilled for your viewing pleasure!

Nothing -- and we mean nothing brings on those warm mushy feeling like a huge dose of animal cuteness! We scoured the internet to bring you the cutest animal pictures of the week! Bringing you cuteness every week - stay tuned for next week's dose! If you missed last week's dose, and you need a cuteness overload, check out last week's here.

Over a phone call from Kolkata, Vikram Rajan*, an audio engineer and guitarist formerly based out of Mumbai, wants us to listen to a track that he has composed. It's available on Soundcloud and, as we stream it, we more or less agree that its flavour of electronica-jazz could accompany a languorous Sunday evening. "For a long time, I had been unable to come up with something good. And, then, I composed this around March while I was microdosing and sometimes, megadosing on acid," says Rajan.

The 33-year-old is referring to a way-of-life that's effectively snapping the ties between drug abuse and the creative arts. This is a lifestyle experiment that some of the brightest techies in Silicon Valley are engaging in, and has got psychiatrists and anti-drug crusaders distraught. "From a 100 mics paper, I take about 20 mics, twice a week, giving the doses a 2-3 days gap. The effects of acid last for about six hours for me," says Rajan, who started experimenting with drugs as a teenager.

After a litany of prescriptions failed to control her mood swings and depression, Ayelet Waldman found relief in LSD. The former federal public defender authored A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life, in 2016. She wrote: "(It) made room in my mind not necessarily for joy, but for insight. It allowed me a little space to consider how to act in accordance with my values, not just react to external stimuli. This, not the razzle-dazzle of pleasure, was its gift." Pic/Getty Images

In need of a quick glossary before we proceed? Acid is officially called Lysergic Acid Diethylamide (LSD), a psychedelic drug banned in India, the possession of which can lead to imprisonment from one to 20 years under the Narcotic Drugs and Psychotropic Substances Act. LSD is often illegally sold in the form of stamps, with the hallucinogen embedded on blotter paper. Mics is micrograms, that's one-millionth of a gram. A microdose is when you have about one-tenth of a recreational 'party' dose, which starts at about 200 mics.

"With microdosing, you are not tripping — this is not a trip. The euphoria isn't there. It's not about feeling good, it's about calmness," continues Rajan. Microdosing first hit headlines after Steve Jobs' passed away in 2011, when a number of inspiring tales on how LSD became the new go-to substance for enhanced performance by tech employees hit the net. Espresso became passé. 'Flow states' were the new yoga. While Jobs did more than just microdose (he was known to have gone all the way), Silicon Valley techies are reportedly doing acid in quantities such that their effects are 'sub-perceptual', where you won't "see stuff" but you harness its "positive" effects.

A dropper with CBD cannabis oil, used for medicinal purposes. Initial research in the area has shown that patients can reap the benefits without its full-blown 'high' effects

Paul Austin, founder of The Third Wave, where you will find a manifesto on microdosing, defines it as, "the act of integrating sub-perceptual doses of psychedelics, such as LSD or Psilocybin Mushrooms, into your weekly routine for higher levels of creativity, more energy, increased focus, and improved relational skills." The Third Wave, according to Austin, follows the first two waves, in which psychedelics were used indigenously for thousands of years, and then, in the 60s and 70s, when they were a part of American counterculture. Austin writes that The Third Wave is upon us, "brought about by recent developments in cannabis legalisation and psychedelic research — and it will change the way mainstream culture perceives psychedelic use."

Classically acid, now weed
For Rajan, however, it wasn't sub-perceptual Silicon Valley that got him to ration his 100 mics stamps, each of which costs about R2,000. It was simply a matter of demand and supply. Mumbai had better stuff than Kolkata, and more availability. Microdosing has classically been associated with LSD, but now has been extended to cannabis as well. Austin's website has guided instructions for microdosing on nine drugs, including cannabis and ayahuasca. Mumbai-based communications officer Varna Kumar*, 25, smokes a mandatory post-work joint every night in order to cope with anxiety and panic attacks. "I feel I have worked enough through the day, without much time to understand what I am going through. At night, when I am by myself, I smoke a small joint to achieve REM sleep," she says. The joint, a mix of two strains, sativa and indica, help her body relax. It makes her anxiety seem defeatable, is how she describes it. Her counsellor, who also smokes up, has not advocated this as a coping mechanism. "It's different from when I am smoking up recreationally during the weekend or when I am away on a vacation. I will do three to four joints when I have nothing to take care of," she says.

Rajan doesn't buy it. He offers an example that may be best contemplated upon or contested by those who have done both LSD and cannabis. "With weed, you are either stoned, or you are not. You will need to smoke up as soon as the high wears off. When you get stoned, your mind becomes passive. But, microdosing on LSD allows you to be calm enough to multitask, allowing a lot of information to be funnelled into your brain easily. You are alert, you are awake," he says, adding, "What is LSD all about? When you start tripping, you see a shift in perspective." You need not agree with Rajan, as he himself says, "We are all chemical reactions", with each of us reacting differently to drugs.

Covert, not convenient
Microdosing will often be compared to that hard-earned and well-deserved one drink after work hours. It's nothing like that, microdosers will tell you, and so will psychiatrists and rehab therapists. For one, microdosing has none of the ease of getting a drink at your favourite pub. You will be persecuted in your search for your creative spell or a calmer mind. Next, it's not even like getting a drug prescription that your GP advises you to have for the course of a fortnight. Kumar and Rajan know it all too well. Microdosing means self-experimentation, knowing when you are crossing the threshold into recreational high dosages. Cannabis, for instance, is best microdosed through edibles, like space brownies, which are available legally in some parts of the world. It's probably the reason why microdosing is yet to take on Silicon Valley proportions in India. "Here, we don't often get to know what strain of cannabis we are using, or where it is sourced from," says Kumar. Saying "this stuff is craazzyy" is, therefore, not enough if you want to microdose. "If you are living with family, it's hard to make edibles. All this means that the convenience factor associated with a drink is not the same with this covert process," she adds.

The idea of the junkie, with matted hair and piercings, is a stereotype that microdosing is replacing. It's no longer cool to be a junkie, especially in the vegan-conscious, gluten-free, aerial yoga health lifestyle that we are seeing around us. Microdosing may be the most metrosexual among the various kinds of drug use, and it carries the allure of high-performance and alleviation of mental health issues, with published studies to back these up. But doctors and psychiatrists are warning us about the glamourisation of microdosing, even as research to mainstream it for mental health is going on. Psychiatrist Dr Samir Parikh says, "Microdosing encourages the thought process that you need a drug for enhanced performance or better creativity or to calm your nerves. This will mean that students microdose before exams, athletes before a run, couples before a wedding, and the next thing you know, because someone has to attend a birthday bash. There is no end to important situations in life. We are making people believe that a student could have scored an additional five marks in an exam had she just microdosed. Can you imagine the perils of this philosophy?" he says. He backs this up with the number of risks associated with prolonged drug abuse, such as a permanent change in brain circuitry, cerebrovascular diseases, and panic attacks.

Then there are those who will argue that moderation as 'one-drink-a-day' is more addictive than the weekend drunken revelry. Is addiction, even in microdoses, still addiction, where the brain searches for rewards compulsively? Kumar disagrees. "Microdosing is the difference between dependence and addiction. For example, I am dependent on a cab to take me to the station. Can I get through my day without it? Can I walk to the station? Yes, I can. That's what microdosing is. I can get through my day without a joint, but a joint just makes it a little easier," she says.Psychiatrist Dr Yusuf Merchant, who runs a rehabilitation centre at Kalyan, says microdoses pose the risk of turning into overdoses. "With any drug, the body learns to metabolise it faster. Which means, that the quantity for a microdose will keep increasing and your hold on reality will keep getting more tangential."

Rajan himself admits to a 'bad trip'. LSD users will tell you that recreational doses are best done in settings that you feel comfortable in, to enjoy, or cope, with the hallucinations. With microdosing, you are headed into your office or your studio to function better. Rajan had once taken more than a microdose, leading him to have a panic attack, the kind where he couldn't even see his hands. The golden rule, he says, is that if you don't go on a full trip, you will never know what a microdose is.

That ailing pain
The push for microdosing is coming from a quarter where its future seems to be most secured — pain management. Mumbai-based homemaker Susheela Kamath*, 48, was diagnosed with stage II breast cancer a couple of years ago, and having undergone nearly a year's worth of chemotherapy and radiation, the accompanying pain and nausea, were all too real. Her daughter provided her with high-grade hash oil. The dealer provided her with a tiny spoon, the kind that you are handed inflight to stir your coffee with. "I had to initially understand, through a lot of trial and error, by gauging my mother's mood, on what a microdose for her would be. Hash oil is very potent," says the daughter.

A little drop of it on her toast every day, helped Kamath cope with pain. "From the third day to the tenth day after chemotherapy, my mother would have about three to four spoons a day, and, on other days, just half a spoon," says the daughter. Coping with the pain meant she could do more during her day, and also have an appetite. Now, months after she has wound up chemotherapy and radiation, she has bid adieu to the prescription drugs that came along with it, and the hash oil as well, without yearning for that high. Unfortunately, unlike medical grade marijuana that is available in some countries, and still not permitted in India, the daughter did not know if the oil had cannabidiol (CBD), which gives marijuana its medical properties, or tetrahydrocannabinol (THC) which gives you the "high".

Dr Kailash Kothari, interventional spine and pain management specialist at Fortis Hospital, Mulund, says that there is not enough evidence to either prove or disprove that microdosing on cannabis can help with pain management, the way opioids, such as morphine, act on the nervous system. "Do cannabinoids work like tranquilisers or do they have long-term effect? There is not enough research as of now," he says, adding, "Getting dependent on these takes a lot of time and not something that can happen in about 15 days of use." In the meanwhile, you can enjoy a night of quiet or a better track on Soundcloud by rationing your stash. But, is it short-term solace or long-term abuse?

*All names have been changed on request to protect identity

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